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2
 3

Cryostasis
Revival
The Recovery of Cryonics Patients through Nanomedicine

Robert A. Freitas Jr.

Senior Research Fellow
Institute for Molecular Manufacturing
Palo Alto, California USA
 4

Cryostasis Revival

The Recovery of Cryonics Patients through Nanomedicine

© 2022 Robert A. Freitas Jr.

All Rights Reserved. No part of this publication may be reproduced or transmitted in any form or
by any means, electronic or mechanical, including photocopying, recording, or any other
information storage and retrieval system, without prior permission in writing from the publisher.

Published in the United States by Alcor Life Extension Foundation, 7895 E. Acoma Drive #110,
Scottsdale, Arizona, USA

https://www.alcor.org/

Printed by Thomas Group Printing in the United States

ISBN: 000-0-0000000-0-0
First Edition
 5

To all who love life’s adventure,

and seek its unbounded continuation
6
 7

Table of Contents
Table of Contents .............................................................................................................. 7

List of Tables ................................................................................................................... 15

Foreword by Gregory M. Fahy, Ph.D. .......................................................................... 17

Acknowledgements ......................................................................................................... 21

1. Introduction ................................................................................................................ 23
1.1 Scientific Rationale for Human Cryopreservation ....................................................... 28
1.2 Medical Nanorobotics ...................................................................................................... 30
1.2.1 Respirocyte-Class Nanorobots.................................................................................... 34
1.2.2 Microbivore-Class Nanorobots ................................................................................... 37
1.2.3 Chromallocyte-Class Nanorobots ............................................................................... 40
1.2.4 Vasculoid-Class Nanorobots....................................................................................... 43
1.2.5 Advantages of Medical Nanorobots ........................................................................... 43
1.3 Atomically Precise Manufacturing of Medical Nanorobots ......................................... 49
1.3.1 Mechanosynthesis ....................................................................................................... 49
1.3.2 Nanofactories .............................................................................................................. 52
1.4 Will Revivals Occur? ....................................................................................................... 56
1.5 Organization of this Book................................................................................................ 58

2. Personal Identity and Cryostasis Revival ................................................................ 59

2.1 Recovery of Personal Identity ......................................................................................... 60
2.1.1 Information-Theoretic Death ...................................................................................... 60
2.1.2 Structural Basis for Long-Term Memory and Personality ......................................... 62
2.1.3 How Much Personal Identity Can Be Recovered? ..................................................... 69
2.1.4 Neurotransmitter Concentrations and Personal Identity ............................................. 77
2.1.5 Other Elements of Personal Identity ........................................................................... 79
2.1.6 Choosing the Correct Method for Revival .................................................................. 85
2.2 Previously Proposed Technical Cryopreservation Revival Scenarios ......................... 87
2.2.1 Immortality Now (Cooper, 1962) ............................................................................... 88
2.2.2 Robot Surgeons of the Future (Ettinger, 1964)........................................................... 90
2.2.3 Viral-Induced Repair (White, 1969) ........................................................................... 92
2.2.4 Anabolocytes: Artificial White Cells for Cryoinjury Repair (Darwin, 1977) ........... 94
2.2.5 Artificial Macrophages, Repair Nets, and the Chrysalis (Donaldson, 1981, 1988) .... 96
2.2.6 Cryonics Revival using Nanomachinery (Drexler, 1986)........................................... 97
2.2.7 Cell Repair Nanorobots (Wowk, 1988) ...................................................................... 99
2.2.8 Nanorobotic Brain Repair with Biological Body Growth (Darwin, 1988) ............... 101
2.2.9 Molecular Brain Repair (Merkle, 1989-1995) .......................................................... 103
2.2.10 Nanotechnological Repair of Frozen Brain (Fahy, 1991) ....................................... 105
2.2.11 SCRAM Reanimation (Soloviov, 1994-1998)........................................................ 108
2.2.12 Reanimation Process (Drexler, 1998) ..................................................................... 109
2.2.13 Low-Temperature Operation of Nanorobots (Freitas, 1999-2007)......................... 110
 8

2.2.14 Revival Scenario Using Molecular Nanotechnology (Merkle and Freitas, 2008) .. 112
2.2.15 Three Methods for Cryonics Revival (Merkle, 2018) ............................................ 116

3. Accumulated Damage to the Cryopreserved Human Body ................................. 119

3.1 Pre-Mortem Somatic Damage....................................................................................... 119
3.2 Post-Mortem Ischemic Damage .................................................................................... 121
3.2.1 Energy Failure, Ionic Imbalance, and Excitotoxicity ............................................... 122
3.2.2 Nitrosative Stress ...................................................................................................... 124
3.2.3 Inflammation............................................................................................................. 125
3.2.4 Protein, RNA, and DNA Stability ............................................................................ 127
3.2.5 Apoptosis, Necrosis, and Structural Degradation ..................................................... 129
3.2.6 White Matter Damage............................................................................................... 132
3.2.7 Histological Ultrastructural Change ......................................................................... 132
3.2.8 Ischemic Damage in the Cryonics Context............................................................... 138
3.3 Perfusion Damage .......................................................................................................... 139
3.3.1 Endogenous Perfusion Damage ................................................................................ 139
3.3.2 Iatrogenic Perfusion Damage.................................................................................... 143
3.4 Freezing or Vitrification Damage ................................................................................. 144
3.4.1 Biochemical and Biophysical Cold Injury ................................................................ 145
3.4.2 Non-Fracture-Related Mechanical Injury ................................................................. 155
3.4.3 Fracture-Related Mechanical Injury ......................................................................... 158
3.5 Cryogenic Storage Damage ........................................................................................... 163
3.6 Rewarming Damage....................................................................................................... 168

4. Plan A: Nanorobotic Revival via Conventional Cell Repair............................... 177

4.1 Macrovascular Scan....................................................................................................... 181
4.1.1 Magnetic Resonance Angiography ........................................................................... 182
4.1.2 Computed Tomography Angiography ...................................................................... 186
4.1.3 Ultrasound Angiography .......................................................................................... 192
4.1.4 Other Conventional Millimeter-Resolution Techniques ........................................... 196
4.2 Macrovascular Excavation ............................................................................................ 200
4.2.1 Cartographic Excavation........................................................................................... 200
4.2.2 Exploratory Excavation ............................................................................................ 207
4.3 Microvascular and Related Scans ................................................................................ 208
4.3.1 Gigahertz Acoustic Microscopy ............................................................................... 210
4.3.2 Terahertz Infrared Imaging ....................................................................................... 213
4.3.3 Optical Coherence Tomography ............................................................................... 214
4.3.4 Confocal Microscopy................................................................................................ 215
4.3.5 High-Resolution X-Ray Microtomography .............................................................. 216
4.4 Microvascular and Related Excavations...................................................................... 216
4.4.1 Capillary, Lymphatic, and Crackface Void Excavation ........................................... 216
4.4.2 Organ and Tissue Surface Perimeter Excavation...................................................... 217
4.4.3 Extracellular Ice Excavation ..................................................................................... 218
4.5 Recondition and Map Exposed Ice Surfaces ............................................................... 218
4.5.1 Clear Excavation Debris from all Exposed Ice Surfaces .......................................... 219
4.5.2 Recondition Exposed Ice Surfaces ........................................................................... 220
 9

4.5.3 Sensor-Driven Ice Peel ............................................................................................. 221

4.5.4 Geometrical Mapping ............................................................................................... 221
4.5.5 Biochemical Mapping ............................................................................................... 222
4.5.6 Locate and Identify Vascular Faults ......................................................................... 223
4.5.7 Locate and Identify Crackface Fracture Planes ........................................................ 223
4.6 Install Vasculoid ............................................................................................................. 224
4.6.1 General Description of Vasculoid............................................................................. 225
4.6.2 Arteriovenous Emplacement..................................................................................... 230
4.6.3 Crackface Voids........................................................................................................ 231
4.6.4 Lymphatic Vasculature and Tissue Perimeter Surfaces............................................ 234
4.6.5 Cryorevival-Specific Equipment .............................................................................. 235
4.7 Submicron Tissue Scan.................................................................................................. 236
4.7.1 Submicron Acoustic Scanning .................................................................................. 237
4.7.2 Optical Microscopy .................................................................................................. 239
4.7.3 Electron Microscopy ................................................................................................. 241
4.7.3.1 Low Voltage Electron Microscopy ..................................................................................242
4.7.3.2 Cryogenic Electron Microscopy .......................................................................................243
4.7.3.3 Transmission Electron Cryomicroscopy ..........................................................................244
4.7.3.4 Electron Cryotomography ................................................................................................244
4.7.4 Direct Chemohaptic Sensing .................................................................................... 245
4.8 Compute Whole-Body Repair Plan .............................................................................. 245
4.8.1 Analysis of Scan Data for Cryonics Repair .............................................................. 246
4.8.2 Maximum Likelihood Estimation ............................................................................. 251
4.8.3 Creating Computational Models to Direct Repairs ................................................... 255
4.8.4 Computational Requirements for Repair Simulations .............................................. 258
4.8.5 Data Storage and Computational Processing Requirements ..................................... 260
4.9 Prethaw and Crackface Fusion ..................................................................................... 262
4.9.1 Prethaw Warming ..................................................................................................... 263
4.9.2 Crackface Fusion ...................................................................................................... 265
4.10 Molecular Extraction ................................................................................................... 268
4.10.1 Targeted Extraction ................................................................................................ 272
4.10.1.1 Oxygen ...........................................................................................................................276
4.10.1.2 Glucose and ATP ...........................................................................................................279
4.10.1.3 Cell Metabolites and Leaked Blood Plasma Components ..............................................282
4.10.1.4 Free Ions .........................................................................................................................286
4.10.1.5 Signaling Molecules .......................................................................................................288
4.10.1.6 Drugs ..............................................................................................................................292
4.10.1.7 Cryoprotectants ..............................................................................................................296
4.10.1.8 Other Potential Extraction Targets .................................................................................300
4.10.1.9 Summary of Extraction Mechanisms and Prioritized Molecular Targets .......................305
4.10.2 Alternative to Targeted Extraction: Tissue Washout ............................................. 309
4.11 Reseal Plasma Membrane Compartments and Rehydrate ...................................... 311
4.11.1 Restore Damaged Cell Plasma Membranes ............................................................ 312
4.11.2 Repair Improperly Rejoined Fracture Face Plasma Membranes ............................ 315
4.11.3 Cell Rehydration and Extracellular Water Transfers .............................................. 316
4.12 Conventional Cellular and Tissue Repair .................................................................. 317
4.12.1 Remove Unwanted Cells and Microbodies............................................................. 318
4.12.1.1 Extracellular Vesicles .....................................................................................................318
4.12.1.2 Red Cells and Platelets ...................................................................................................319
 10

4.12.1.3 Errant White Cells ..........................................................................................................321

4.12.1.4 Bacteria ..........................................................................................................................322
4.12.1.5 Other Pathological Microbes ..........................................................................................323
4.12.1.6 Cancer Cells ...................................................................................................................324
4.12.2 Inspect and Repair Existing Cells ........................................................................... 326
4.12.2.1 Preliminary Cell Inspection and Small Debris Cleanup .................................................326
4.12.2.2 Cell Nucleus Repair or Replacement .............................................................................327
4.12.2.3 Non-Nucleus Organelles ................................................................................................330
4.12.2.4 Cytoskeleton and Related Intracellular Components .....................................................333
4.12.2.5 Extract and Replace Maloccupied Membrane Receptors ...............................................335
4.12.2.6 Plasma Membrane and Transmembrane Protein Editing ...............................................337
4.12.2.7 Glycocalyx Repair ..........................................................................................................338
4.12.2.8 Whole-Cell Replacement Option ...................................................................................340
4.12.3 Supplemental Tissue Repair ................................................................................... 341
4.12.3.1 Foreign Object Extraction and Avulsion Wound Repair ................................................341
4.12.3.2 Residual Vascular Repair ...............................................................................................342
4.12.3.3 ECM Reconditioning......................................................................................................343
4.12.3.4 Withdraw Vasculoid from Tissue Perimeter Surfaces....................................................346
4.12.4 Supplemental Neural Repair ................................................................................... 346
4.12.4.1 Axonal Repair ................................................................................................................346
4.12.4.2 Neuron Membrane Editing .............................................................................................348
4.12.4.3 Missing Brain Tissue ......................................................................................................350
4.13 Patient Warmup and Molecular Instillation ............................................................. 352
4.13.1 Warm the Patient .................................................................................................... 352
4.13.2 Instill Nonactivating Molecules via Vasculoid ....................................................... 353
4.13.3 Whole-Body Fluid Check and Perimeter Surface Cleanup .................................... 354
4.13.4 Instill Storage Nanorobots that Carry Activating Molecules .................................. 355
4.14 Uninstall Vasculoid and Finish Repairs ..................................................................... 356
4.14.1 Manufacture Replacement Blood ........................................................................... 356
4.14.1.1 Blood Substitute .............................................................................................................357
4.14.1.2 Manufactured Natural Blood ..........................................................................................358
4.14.2 Uninstall Vasculoid and Transfuse Blood Substitute ............................................. 360
4.14.3 Initiate Normal Metabolism and Remove Storage Nanorobots .............................. 364
4.14.4 Replace Blood Substitute with Manufactured Natural Blood................................. 365
4.15 Patient Wakeup and Post-Awakening Protocols ....................................................... 366
4.16 Summary of Conventional Cell Repair ...................................................................... 371
4.17 Why Biological Methods of Cryostasis Revival are Likely Infeasible ..................... 373

5. Plan B: Nanorobotic Revival via Molecular Reconstruction .............................. 378

5.1 Extract Nonstructural Bulk Materials ......................................................................... 379
5.2 Molecular Reconstruction of a New Replacement Body ............................................ 380
5.2.1 Destructive Molecular Scan ...................................................................................... 381
5.2.1.1 Abstraction of Water Molecules .......................................................................................383
5.2.1.2 Positional Disassembly of Biomolecules .........................................................................386
5.2.1.3 Destructive Molecular Scan System Scaling ....................................................................395
5.2.2 Computational Cost of Fault Correction ................................................................... 400
5.2.2.1 Initial Scan File ................................................................................................................400
5.2.2.2 Corrected Scan File ..........................................................................................................403
5.2.2.3 Optional Synthetic Conversion File .................................................................................406
5.2.3 Print Replacement Patient Body ............................................................................... 407
5.2.3.1 Cryogenic 3D Atomic Print..............................................................................................408
 11

5.2.3.2 Cryogenic 3D Molecular Print .........................................................................................415

5.2.3.3 Fluidic 3D Cell Print ........................................................................................................420
5.2.3.3.1 Planar Tissue Printing ...............................................................................................422
5.2.3.3.2 Scaffolded Tissue Printing........................................................................................425
5.2.3.3.3 Nanorobot-Guided Embryonic Growth ....................................................................427
5.2.3.4 Virtual 3D Bit Print (an “Upload”) ..................................................................................428
5.2.3.4.1 Upload from Revived Biological Intermediate (a “Live Transfer”) .........................432
5.2.3.4.2 Physical Instantiation of Virtual Body (a “Download”) ...........................................433
5.3 Molecular Reconstruction of the Original Body ......................................................... 435
5.3.1 Nondestructive Molecular Scan ................................................................................ 437
5.3.2 Initial and Corrected Scan Files ................................................................................ 441
5.3.3 Repair Original Patient Body.................................................................................... 443
5.3.3.1 Cryogenic Molecular Exchange Repair............................................................................443
5.3.3.2 Fluidic Molecular-Informed Cell Repair ..........................................................................445
5.4 High-Speed Molecular Reconstruction ........................................................................ 445
5.5 Summary of Molecular Reconstruction ....................................................................... 447

6. Replacement Bodies for Neuro Patients ................................................................ 454

6.1 Fabricate and Attach Normothermic Replacement Body .......................................... 457
6.1.1 Grown Acephalic Autologous Body ......................................................................... 458
6.1.1.1 Cephalon Attached to Grown Trunk ................................................................................464
6.1.1.2 Trunk Grown onto Cephalon ............................................................................................467
6.1.1.3 Cephalon Attached to Donor Trunk .................................................................................468
6.1.2 Nanofabricated Acephalic Autologous Body ........................................................... 470
6.1.3 Head Caddy or Biocompatible Artificial Body ........................................................ 471
6.1.4 Cost of Replacement Body for Neuro Patients ......................................................... 477
6.2 Separately Stored Cryopreserved Trunk..................................................................... 480

7. Alternatives, Validations, and Research Opportunities ....................................... 482

7.1 Alternative Pathways to (and from) Biostasis ............................................................. 482
7.1.1 Straight-Freeze and Poorly-Perfused Cryopreservation Patients .............................. 483
7.1.2 Intermediate Temperature Storage............................................................................ 485
7.1.3 Clathrate Cryopreservation ....................................................................................... 488
7.1.4 Persufflation and Vascular Cryofluids ...................................................................... 489
7.1.5 Chemical Fixation ..................................................................................................... 491
7.1.6 Suspended Animation ............................................................................................... 496
7.1.6.1 Human Hibernation ..........................................................................................................498
7.1.6.2 Chemical Biostasis ...........................................................................................................501
7.1.6.3 Cryptobiosis .....................................................................................................................503
7.1.6.4 Hypothermic Biostasis .....................................................................................................504
7.1.6.5 Nanostasis (Warm Biostasis) ............................................................................................506
7.1.7 Revival from Frozen Genetic Material ..................................................................... 509
7.1.8 Whole-Body Backups ............................................................................................... 510
7.2 Validation of Cryopreservation Revival Procedures .................................................. 512
7.2.1 Animal Testing Should Suffice................................................................................. 512
7.2.1.1 Simple Memory ................................................................................................................513
7.2.1.2 Complex Memory ............................................................................................................513
7.2.1.3 Personality ........................................................................................................................514
7.2.1.4 Personal Identity...............................................................................................................515
7.2.1.5 Nanorobot- and WBE-Based Animal Validations ............................................................518
 12

7.2.2 Human WBE Testing ................................................................................................ 521

7.3 Future Research Opportunities .................................................................................... 524

Appendix A. Society for Cryobiology No Longer Openly Hostile to Cryonics ...... 526

Appendix B. Cryopreservation in Science Fiction (1846-2021) ............................... 528

Appendix C. Early Nanorobotic Revival Concepts (G.M. Fahy, 1991) .................. 554

Appendix D. Cell Mills ................................................................................................ 562

D.1 Biomolecule Synthesis Module ..................................................................................... 563
D.1.1 Generic Organic Molecules ..................................................................................... 563
D.1.1.1 Conventional Manufacturing of Generic Organics ..........................................................563
D.1.1.2 Molecular Manufacturing of Generic Organics ...............................................................565
D.1.2 Personalized Organic Molecules.............................................................................. 572
D.1.2.1 Consensus Genomic Sequence ........................................................................................572
D.1.2.1.1 Genome Sampling ...................................................................................................573
D.1.2.1.2 Chromosome Sequencing ........................................................................................577
D.1.2.2 Manufacturing Personalized DNA ..................................................................................581
D.1.2.3 Manufacturing Personalized Proteins and Carbohydrates ...............................................584
D.2 Cytocomponent Assembly Module .............................................................................. 588
D.2.1 Cell Membranes ....................................................................................................... 589
D.2.2 Macromolecular Organelles ..................................................................................... 591
D.2.3 Vesicular Organelles ................................................................................................ 596
D.2.4 Membraneous Organelles ........................................................................................ 603
D.2.5 Cell Nucleus............................................................................................................. 607
D.3 Cell Assembly Module .................................................................................................. 611
D.3.1 Cell Assembly Process............................................................................................. 613
D.3.2 Cell Mill System Scaling ......................................................................................... 616

Appendix E. Additional Plateable Tissue Surfaces ................................................... 620

Appendix F. Chemohaptic Atomic Scanning and Identification ............................. 624

F.1 Chemohaptic Analysis ................................................................................................... 624
F.1.1 Scanning Probe Microscopy ..................................................................................... 624
F.1.2 Structure Determination by AFM ............................................................................. 626
F.1.3 Element Typing of Atoms by AFM .......................................................................... 628
F.1.4 Element Typing of Functional Groups by AFM....................................................... 630
F.1.5 Chemohaptic Analysis of More Difficult Cases ....................................................... 633
F.2 Molecular Assay System Scaling .................................................................................. 633
F.2.1 Minimum Size of Lab Module for Chemohaptic Analysis ...................................... 634
F.2.2 Size and Performance of a Molecular Assay System ............................................... 636

Appendix G. Historical and Future Commercial Electricity Prices ....................... 638

Appendix H. Binding Site Design ............................................................................... 640

H.1 Binding Site Design for Carbon Dioxide Molecules................................................... 642
 13

H.2 Binding Sites for Other Simple Molecules .................................................................. 645

H.3 Binding Sites for Cryoprotectant Molecules .............................................................. 649

Appendix I. Cell Metabolites ...................................................................................... 652

Appendix J. Blood Plasma Leakage Molecules ......................................................... 656

Appendix K. Free Ions ................................................................................................. 662

Appendix L. Cryoprotectants ..................................................................................... 664

Appendix M. Nanorobot Extraction from the Body ................................................. 666

Appendix N. Neuropreservation and Whole-Body Preservation Options .............. 670

Appendix R. List of Future Research Topics Supporting Cryostasis Revival ....... 672

Image Credits ................................................................................................................ 694

14
 15

List of Tables

Table 1. Average number of neurons present, and percentage neuron losses, in three specific
brain regions during various stages of Alzheimer’s dementia....................................................... 73
Table 2. Estimated neural circuitry loss during typical acute ischemic stroke ............................. 74
Table 3. Estimated natural endoradioactivity in the human body (70-kg human adult) ............ 165
Table 4. High-frequency acoustic attenuation coefficients ........................................................ 212
Table 5. Number, mass and volume of baseline vasculoid system components ........................ 227
Table 6. Plateable surfaces of the lymphovascular system......................................................... 234
Table 7. A few representative databases and datasets containing information about
neuroanatomical connections ...................................................................................................... 250
Table 8. Components of M22 cryoprotectant solution commonly employed in human
cryopreservation .......................................................................................................................... 297
Table 9. Number, volume, mass, and power draw of sorting rotors needed to extract prioritized
extraction targets from interstitial and intracellular fluid compartments, in one hour ................ 306
Table 10. Approximate number of non-nucleus replacement intracellular organelles needed for a
70 kg human whole-body cryopreservation patient .................................................................... 331
Table 11. Approximate quantification of cytoskeletal components possibly needing repair ..... 334
Table 12. Nanorobot count and treatment time to execute nanorobotic tasks for the Third
Alzheimer Protocol (neural reconstruction) ................................................................................ 351
Table 13. Nominal list of conventional repair tasks for human cryopreservation revival, with
estimated task durations for whole-body and neuro patients ...................................................... 371
Table 14. Estimated gross molecular contents of a typical 20 μm human cell........................... 396
Table 15. Estimated memory, CPU requirements, and cost to run an emulation of the human
brain, body, and living environment, at the specified level of emulation fidelity ....................... 430
Table 16. Molecular reconstruction tasks and task durations for human cryopreservation revival
using destructive and nondestructive molecular scan protocols .................................................. 448
Table 17. Estimated cost of revival from human cryopreservation in various scenarios for whole-
body and neuro cases, for costly/cheap energy and manufacturing prices .................................. 451
Table 18. Maximum molecular nutrient transport requirements for an isolated biological
cephalon, estimated as 20% of whole-body requirement ............................................................ 474
Table 19. Estimated U.S. average 2020 transplant cost, per procedure ..................................... 478
Table 20. Figures of merit for DNA sequencing system productivity for three sequencing
technologies ................................................................................................................................. 581
Table 21. Mass % biochemical composition of organelle and cell membranes. ........................ 591
Table 22. Number of organelles to be installed in a typical 8000 μm3 tissue cell ...................... 614
Table 23. Summary of exemplar cell mill volume, mass, and power requirements................... 617
 16

Table 24. System parameters for a Lab Module that performs a single-molecule structural and
elemental characterization. .......................................................................................................... 635
Table 25. Gas molecule concentration in ambient U.S. dry atmosphere, their binding energy in a
simple pore of a molecular filter, and their concentration in the resulting filtrate. ..................... 644
 17

Foreword by Gregory M. Fahy, Ph.D.

Dr. Greg Fahy is a complex systems cryobiologist and the Executive Director and Chief Scientific Officer
of the cryobiological biotechnology company, 21st Century Medicine, Inc. His scientific research has been
recognized by the Society for Cryobiology, which made him a Fellow in 2014. 1 His comments are his own
and do not reflect the views of any affiliated organization.

A Glimpse of the Future

This is a book that is ultimately about the technical feasibility of cryonics. Cryonics is the practice of
preserving individuals at cryogenic temperatures today for possible revival in the future. Human
cryopreservation could in theory have several uses, ranging from the exploration of the cosmos in the
distant future to “medical time travel” in the present. Regarding the latter, if medical conditions that are
incurable today, including even the “medical condition” of being preserved by today’s imperfect methods
under often imperfect circumstances, will become curable in the future, then putting the course of today’s
fatal illnesses on hold by cryopreservation may provide hope for those who are deemed to be beyond hope
by today’s medicine. 2

But “if” is a large word in this context. Without a clear answer, cryonics has been inevitably controversial.
In the meantime, in the absence of being able to foretell the future, cryonics has historically been defended
on the basis of two fundamental empirical observations. 3

The first observation is the fact that humans have been creating more and more advanced technology, and a
deeper and deeper understanding of the world, since our inception as a species, and that this creative
process of discovery and improvement is likely to continue. Carried to its logical conclusion, it seems
inevitable that, if the species survives and progress is allowed to continue indefinitely, we will eventually
acquire the ability to accomplish any goal that does not violate physical and economic law.

The second observation is that cryobiology, the study of the effects of low temperatures on living systems,
teaches us that viable mammalian cells can be stored for very long times at cryogenic temperatures and
then revived successfully in a distant future. For example, present estimates suggest that it would take
32,000 years for background radiation to kill 90% of cultured cells after freezing to low temperatures. 4
Neurons in the brain are less sensitive to radiation damage than tissue culture cells and so might last longer,
and storage times may also be extended by enhanced post-thawing DNA repair alone and by the presence
of very high concentrations of cryoprotective agents, which are used in ice-free cryopreservation by
vitrification 5 and may be radioprotective. 6 And even longer survival times have been claimed under natural
conditions. 7

1
https://en.wikipedia.org/wiki/Greg_Fahy.
2
Ettinger RCW. The Prospect of Immortality. New York: Doubleday; 1964.
3
Ibid.
4
Ashwood-Smith MJ, Grant E. Genetic stability in cellular systems in the frozen state. In: Elliott K, Whelan J, editors. The
Freezing of Mammalian Embryos. Amsterdam: Elsevier / Excepta Medica /North-Holland 1977. p. 251-67.
5
Fahy GM, Wowk B. Principles of ice-free cryopreservation by vitrification. In: Wolkers WF, Oldenhof H, editors.
Cryopreservation and freeze-drying protocols (Methods Mol Biol 2180). New York: Humana Press; 2021. p. 27-97.
6
Ashwood-Smith MJ. Current concepts concerning radioprotective and cryoprotective properties of dimethyl sulfoxide in
cellular systems. Ann N Y Acad Sci. 1975;27:243-6.
 18

Potentially tens of thousands of years is a long time for technological achievements to accumulate. Even
today, it seems apparent that advances in all areas of science and technology are proceeding at exponential
rates. Some have even projected the arrival of a “singularity”, 8 which is a point in time beyond which
progress becomes so transformational that it is impossible to imagine what it will mean for our experience
of life, just decades from now.

So it does seem relevant to ask: are the tasks that would be required to revive individuals after previous
cryogenic storage with present imperfect techniques forbidden by physical law? The answer depends on
two factors: how much and what kind of damage must be repaired, and what repair capabilities are
possible in principle?

The first question has been addressed experimentally, as reviewed in depth in this book. From the
perspective of cryobiology, there are some positive findings, but also still many unknowns and limitations.
When conventional ice crystal damage to whole organs was prevented by vitrification, a rabbit kidney was
able to support life indefinitely after cooling to -130 ᵒC, rewarming, and transplantation. 9 Regarding the
brain in particular, which is of central importance for the proposition of cryonics, it has been found that, as
Freitas reviews in this book, partially frozen animal brains have registered coherent electroencephalograms
after thawing from -20 ᵒC, 10 frozen hamsters have recovered despite conversion of more than half of their
brain water into ice at -1 ᵒC, 11 and both frozen and vitrified worms have retained memories after rewarming
that were instilled before cryopreservation. 12 Hippocampal slices, also, have been vitrified and rewarmed
with good retention of viability, 13 ultrastructure, 14 electrical responsiveness, 15 and the ability to generate
long-term potentiation. 16 The most direct observations that can be made, however, are those that can be
made on the brains of actual human cryonics volunteers. Beyond the macroscopic studies reviewed in this
book, there has been one study, whose results are presently being analyzed and prepared for publication, on
brain fine structural integrity. 17 Preliminary indications are that brain structure was well preserved on both

7
https://www.livescience.com/63187-siberian-permafrost-worms-revive.html?utm_source=notification.
8
Kurzweil R. The Singularity is Near: When Humans Transcend Biology. New York: Viking; 2005.
9
Fahy GM, Wowk B, Pagotan R, Chang A, Phan J, Thomson B, et al. Physical and biological aspects of renal vitrification.
Organogenesis. 2009;5:167-75.
10
Suda I, Kito K, Adachi C. Viability of long term frozen cat brain in vitro. Nature. 1966;212:268-70. Suda I, Kito K, Adachi
C. Bioelectric discharges of isolated cat brain after revival from years of frozen storage. Brain Research. 1974;70:527-31.
11
Lovelock JE, Smith AU. Studies on golden hamsters during cooling to and rewarming from body temperatures below 0oC.
III. Biophysical aspects and general discussion. Proc Roy Soc, B. 1956;145:427-42.
12
Vita-More N, Barranco D. Persistence of long-term memory in vitrified and revived Caenorhabditis elegans. Rejuvenation
Res. 2015;18(5).
13
Pichugin Y, Fahy GM, Morin R. Cryopreservation of rat hippocampal slices by vitrification. Cryobiology. 2006;52:228-40.
14
Ibid.
15
Fahy GM, Guan N, De Graaf IAM, Tan Y, Griffin L, Groothuis GMM. Cryopreservation of precision-cut tissue slices.
Xenobiotica. 2013;43:113-32.
16
Ibid.
17
Fahy GM, Wowk B, Vargas V, Hixon H, Graber S, Thomson B, et al. Ultrastructural cryopreservation of the mammalian
brain. (in preparation).
 19

the histological and electron microscopic level, and was actually preserved much better than in animal
brains in past studies. Ice formation was successfully avoided in all brain biopsies examined by differential
scanning calorimetry, indicating excellent perfusion of the brain after cardiac arrest and transportation, and
whole brain fracturing was not observed after cooling to -146 ᵒC. These results suggest that, when cryonics
is carried out under favorable conditions, and when ice formation is prevented by vitrification, it has every
appearance of preserving the structure and the molecular inventory of the brain.

However, cryonics is often attempted under poor conditions, and although the effects of disease and
ischemia are reviewed in this book in detail, there is no published information on the effects of these pre-
cryopreservation factors on the outcomes of preparation for cryopreservation (although some unpublished
studies involving 1 hour of warm ischemia followed by 24 hours of cold storage before cryopreservation
have been promising 18). There are also few 19 published studies of human or other mammalian brain
viability after vitrification, and past successful studies involving partial brain freezing 20 did not involve
cooling to temperatures low enough for long term storage. Factors that may affect brain viability after
vitrification (including brain shrinkage, background hypothermic injury, and possibly protein denaturation
by cryoprotective agents 21) have been individually addressed with success in separate model systems, but
whole brain viability studies are lacking. The final reality is that, after all, it is still true that today’s
methods, if applied to the cooling of either a brain or a whole mammal to cryogenic temperatures, even
under good conditions, would not be expected to result in spontaneous recovery, and superimposing
variable degrees of cardiac arrest prior to such experiments would make failure even more likely. In
addition, preserving the brain is far from being the only problem that must be overcome to restore
cryopreserved individuals to life.

Therefore, despite several favorable signs, injury induced by present cryonics procedures cannot be
repaired without highly advanced future repair technologies that can be applied to cryopreserved systems.
Therefore, the second question, pertaining to the ultimate feasibility of these technologies, remains
essential for the evaluation of cryonics, and is fortunately the major issue addressed in this book.

Much has been written previously about the general technical feasibility of what K. Eric Drexler named
“nanotechnology” (and later, “molecular nanotechnology”), which is the atomically precise engineering
and fabrication of molecular machines and molecularly defined materials. Further, the offspring of
nanotechnology, “nanomedicine,” has been explored in overwhelming detail in previous works by present
author Robert Freitas. Ralph Merkle, too, has contributed much to an understanding of the global
feasibility of molecular repair of cryopreserved brains, and other scenarios of repair have been suggested
and are reviewed in depth in this volume. However, the present book is the only resource that
comprehensively puts together the entire picture of nanomedical repair of cryonics patients as only Rob
Freitas can do. “Conventional” nanomedicine must confront modifications to a body that is for the most
part already maintaining its own viability. It is an entirely different problem to repair patients who are in a
solid state at cryogenic temperatures. For that, new tools must be devised, and in this work, Freitas
supplies the closest look we have had so far at what these future tools might include.

18
Fahy GM, et al. Vitrification of whole rabbits under good and compromised conditions. (unpublished observations)
19
Pichugin Y, Marchenko VS, Shilo AV, editors. Bioelectric activity of cryopreserved brain pieces of a rabbit. The 14th
Conference on Preservation of Genetic Resources; 1996; Pushchino: Academpress.
20
Suda I, Kito K, Adachi C. Viability of long term frozen cat brain in vitro. Nature. 1966;212:268-70. Suda I, Kito K, Adachi
C. Bioelectric discharges of isolated cat brain after revival from years of frozen storage. Brain Research. 1974;70:527-31.
Lovelock JE, Smith AU. Studies on golden hamsters during cooling to and rewarming from body temperatures below 0oC.
III. Biophysical aspects and general discussion. Proc Roy Soc, B. 1956;145:427-42.
21
Fahy GM, Wowk B. Principles of ice-free cryopreservation by vitrification. In: Wolkers WF, Oldenhof H, editors.
Cryopreservation and freeze-drying protocols (Methods Mol Biol 2180). New York: Humana Press; 2021. p. 27-97.
 20

Freitas’ approach to repair proceeds in a logical fashion. First, survey the damage. Second, gain access to
what needs to be repaired by tunneling through inconsequential material, particularly in the vascular system
and similar conduits. Third, stabilize structures that must be repaired and install structures necessary for
later repair and more detailed surveys. Fourth, figure out what needs to be done based on what has been
learned. Fifth, start by stabilizing fractures and then warming sufficiently to enable fracture faces to be
fused back together again. And sixth, proceed with the rest of the details (of which there are a great many).
It is hard to argue with this staging of events.

Even while attempting to describe as many details of the repair process as possible, however, it must be
understood that concepts of repair depend on concepts of the damage that requires repair, and, as noted
above, the latter remain incomplete. To his credit, Freitas identifies a myriad of topics worthy of future
research throughout these scenarios, an acknowledgement that the present work is not and cannot be the
final word, but it does not need to be. Extracting and then replacing molecules like glucose and oxygen,
attempting to artificially manipulate osmosis, and artificially resealing membranes with altered
semipermeability may all be unnecessary. However, if they are technically possible, then it becomes
plausible that lesser capabilities will be able to do lesser tasks that actually are necessary. If the real goal is
to plumb the depths of the possible, the present volume accomplishes that goal extraordinarily well.

Will the overall possibilities outlined here someday be realized? Will lives be saved? Will new adventures
emerge as the people of the present engage with the entities of the future? Only time will tell. The
proposals in this book cannot by themselves prove that cryonics will succeed, or define precisely what
conditions of preservation will be required for cryonics to succeed. The totality of the arguments presented
does, however, elevate the discussion to an unprecedented level of specificity and detail, and must figure
prominently in further scientific evaluation of the proposal of cryonics.

Cryonics, uniquely, is a present practice that is largely based on the possibilities of future technology, but
the future has always been hard to see. Now, exactly 60 years after cryonics was first proposed in 1962, 22
Freitas has provided a highly concrete glimpse into a future in which a set of definable and technically
defensible future technologies could be equal to the task of repairing virtually any degree of biological
injury associated with cryonics. His new comprehensive and falsifiable framework for debate and
discussion may well lead to less dismissal and more serious consideration of the proposition of cryonics
from this point forward. In that sense, just possibly, cryonics itself, if not yet those who have undergone it,
may be at the threshold of a new awakening.

Gregory M. Fahy, Ph.D.

Corona, California
January, 2022

22
Duhring N. Immortality: Physically, Scientifically, Now. Washington, D.C.: 20th Century Books Foundation; 1962.
 21

Acknowledgements
The author would like to thank Ralph Merkle, Aschwin de Wolf, Tad Hogg, Michael Perry, James Ryley,
Brian Wowk, and Greg Fahy for reading and commenting on earlier drafts of this manuscript, and for many
substantive suggestions that have materially improved the quality and accuracy of the work. Any
conceptual or design flaws, mathematical mistakes, or errors of fact that remain are solely the responsibility
of the author.

The author also thanks Natasha Vita-More for assembling the cover art, Gina “Nanogirl” Miller for
providing several interior illustrations of the nanorobotic vasculoid concept, and Ping Lim for creating an
additional interior illustration of the vasculoid at work.

Special thanks must be extended to: (1) Aschwin de Wolf, for initially proposing that the author should
undertake a more comprehensive analysis of nanorobotic-based cryonics revival than had ever been
attempted before (which turned into this book-length treatment), for constant encouragement throughout
2019-2022 while this book was being written and prepared for publication, and for acting as Alcor’s
production editor for the project; (2) Brian Wowk, for his particularly extensive technical review; and (3)
Greg Fahy, for writing the Foreword and for providing illustrations from his early nanorobotic revival
concepts.

Finally, the author thanks Jill Grasse for doing the graphic design and electronic formatting work on the
book; Michael Benjamin for assistance securing image permissions; and the Alcor Life Extension
Foundation for publishing this book in both print and electronic formats, and for permanently hosting the
latter on their website.
22
 23

1. Introduction
Raising the dead to life is a difficult task. Fortunately for cryonicists, a cryopreserved patient is not
actually “dead”. 23 Rather, the body or brain of a dying cryonics 24 patient is carefully placed into a
condition of cold biological stasis – or “cryostasis” – conceptually not unlike hibernating 25 primates 26 and
bears, 27 or frozen wood frogs 28 and Siberian salamanders, 29 except that some survival-critical damage
exists in the patient’s body, requiring repair. Given the right conditions, all of these animals – including the
human – can return to normal life. Humans are not natural hibernators, so the cryopreserved person will
need technological assistance to accomplish this feat, having previously employed various cryopreservative
interventions to enter the state of biological stasis in the first place. It is the goal of this book to describe, in
general outline, the technological assistance that may be sufficient to allow human beings to successfully
exit the state of cryogenic biological stasis (cryostasis) and resume normal life with their original personal
identity intact – and directions for future research that can help bring this technology to fruition.

This book presents the first comprehensive conceptual protocol for revival from human
cryopreservation, using medical nanorobots.

The prospect of revival 30 is grounded in two grand assumptions: First, that it is possible to cool a human
being to cryogenic temperatures “without fundamentally destroying the essential information underlying
memory and personality in the brain”; and, second, “that medical and scientific progress will continue until
medical resuscitation technology is limited only by physical law.” If both these assumptions are correct,

23
Wowk B. The Death of Death in Cryonics. Cryonics 1988 Jun;9(6):30-37; https://www.alcor.org/docs/cryonics-magazine-
1988-06.txt. Of course, all cryopreserved patients have been pronounced “legally dead” by the appropriate local medical
authorities prior to cryopreservation; https://www.alcor.org/library/the-legal-status-of-cryonics-patients/.
24
“Cryonics is the practice of preserving life by pausing the dying process using subfreezing temperatures with the intent of
restoring good health with medical technology in the future.” https://www.alcor.org/.
25
Hadj-Moussa H, Storey KB. Bringing nature back: using hibernation to reboot organ preservation. FEBS J. 2019
Mar;286(6):1094-1100; https://febs.onlinelibrary.wiley.com/doi/full/10.1111/febs.14683.
26
Storey KB. The Gray Mouse Lemur: A Model for Studies of Primate Metabolic Rate Depression. Preface. Genomics
Proteomics Bioinformatics. 2015 Apr;13(2):77-80; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4511782/. See also:
https://en.wikipedia.org/wiki/Fat-tailed_dwarf_lemur#Hibernation.
27
https://en.wikipedia.org/wiki/Hibernation#Bears.
28
https://en.wikipedia.org/wiki/Wood_frog#Cold_tolerance.
29
https://en.wikipedia.org/wiki/Salamandrella_keyserlingii#Description.
30
“Revival” means the restoration to consciousness or life from a depressed, inactive, or unused state that is generally of
indeterminate duration, and best fits the classical intent of direct physical restoration of a human patient from a very-long-term
cryopreservation. “Reanimation” means to restore to a physically active state and is a close synonym for “revival,” but has
unfortunate connotations from horror films; also, “reanimate” is 100 times less popular than “revive” in common usage (i.e.,
1M hits vs. 100M hits on Google). “Resuscitation” also has a similar meaning as “revival” but is generally used in the
medical context of a patient who has been inactive for a much shorter period of time, typically hours or days, or occasionally
months. “Reincarnation” means to be reborn in another body, which would not apply to cryonics cases involving
conventional cell repair (Chapter 4) or to molecular reconstruction of the original body (Section 5.3) but could arguably apply
to molecular reconstruction of a new body (Section 5.2) or to neuro patients who receive an entirely new body (Chapter 6).
“Resurrection” means to restore to life a biological entity that was truly “dead,” presumably in the information-theoretic
sense (Section 2.1.1), e.g., perhaps requiring something like Tipler’s far-future “Omega Point” to re-create all lifeforms in the
universe that have ever lived since the start of time,* and often has religious connotations.
*
Tipler FJ. The Physics of Immortality. Doubleday, New York, 1994; “Chapter IX. The Physics of Resurrection of the Dead
to Eternal Life”; https://www.amazon.com/Physics-Immortality-Modern-Cosmology-Resurrection/dp/0385467990/.
 24

then “the memories and personalities of people preserved by today’s methods should be intact after revival
by future technology, and medical time travel 31 can be used as a bridge to a time when senescence can be
controlled.” 32

In the following pages we will describe exactly how medical nanotechnology may be used to restore
cryonics patients to the viable physical condition they enjoyed prior to being pronounced legally deceased
and prior to being subjected to various cryopreservation procedures. The patient who is revived according
to this criterion may still be “sick” by current medical definitions, but they will not be in imminent danger
of relapse due to their remaining infirmities. Once alive and stabilized, the revived patient can then receive
more conventional nanomedical procedures to restore themselves to full health and youthful vigor, using
medical nanorobots 33 to correct all commonplace medical disease states such as bacterial infections 34 or
genetic defects, 35 up to and including the most challenging ones such as aging 36 and dementia. 37

It is important to note that “[a]ll cryonics patients in long-term storage are ‘cryopreserved’. Since
vitrification is a relatively recent (21st century) procedure in cryonics, not all cryonics patients have been
‘vitrified’. Of the patients that have not been vitrified, some have received some degree of cryoprotection
and others have been ‘straight frozen’….The best way to think about cryopreservation is to imagine a
continuum, ranging from complete freezing without any cryoprotectants, to complete vitrification achieved
through the effective use of cryoprotectants. In the case of a straight freeze, 38 where cryoprotectants
aren’t used at all, ice formation is at its maximum. In the case of complete vitrification 39 there is no ice at
all. In cryonics, the outcome of a case can theoretically be at either of those extremes, but a more typical

31
Wowk B. Medical Time Travel. In: Immortality Institute. The Scientific Conquest of Death. Libros en Red, 2004, pp. 135-
149; https://www.alcor.org/library/medical-time-travel/.
32
Lemler J, Harris SB, Platt C, Huffman TM. The arrest of biological time as a bridge to engineered negligible senescence.
Ann N Y Acad Sci. 2004 Jun;1019:559-63; http://www.alcor.org/Library/pdfs/Lemler-Annals.pdf.
33
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities, Landes Bioscience, Georgetown, TX, 1999;
http://www.nanomedicine.com/NMI.htm. Freitas RA Jr. Nanomedicine, Volume IIA: Biocompatibility, Landes Bioscience,
Georgetown, TX, 2003; http://www.nanomedicine.com/NMIIA.htm.
34
Freitas RA Jr. Microbivores: Artificial Mechanical Phagocytes using Digest and Discharge Protocol. J. Evol. Technol. 2005
Apr;14:55-106; http://www.jetpress.org/volume14/freitas.pdf.
35
Freitas RA Jr. The Ideal Gene Delivery Vector: Chromallocytes, Cell Repair Nanorobots for Chromosome Replacement
Therapy. J. Evol. Technol. 2007 Jun;16:1-97; http://jetpress.org/v16/freitas.pdf.
36
Freitas RA Jr. Chapter 23. Comprehensive Nanorobotic Control of Human Morbidity and Aging. In: Fahy GM, West MD,
Coles LS, Harris SB, eds, The Future of Aging: Pathways to Human Life Extension, Springer, New York, 2010, pp. 685-805;
http://www.nanomedicine.com/Papers/Aging.pdf.
37
Freitas RA Jr. The Alzheimer Protocols: A Nanorobotic Cure for Alzheimer’s Disease and Related Neurodegenerative
Conditions. IMM Report No. 48, June 2016, 433 pp; http://www.imm.org/Reports/rep048.pdf.
38
According to the official case metrics, Alcor patients received a straight freeze in 14% of all cases during 1967-1999* and in
23% of all cases during 2000-2020.†
*
Benjamin M, de Wolf A. Alcor Case Metrics 1967-1999. Cryonics 2021 Qtr III; 42(3):12-18, chart p. 13;
https://www.alcor.org/docs/cryonics-magazine-2021-03.pdf.
†
Benjamin M, de Wolf A. Alcor Case Metrics 2000-2020. Cryonics 2021 Qtr II; 42(2):10-30, chart p. 24;
https://www.alcor.org/docs/cryonics-magazine-2021-02.pdf.
39
https://en.wikipedia.org/wiki/Vitrification#Vitrification_in_cryopreservation and
https://en.wikipedia.org/wiki/Cryopreservation#Vitrification.
 25

outcome is some point in between.” 40 Most of the nanorobot-based revival procedures described in this
book are assumed to be performed on a cryopreserved patient who was well perfused with an appropriate
vitrification cryoprotectant 41 such as M22, 42 then cooled all the way to ~77 K (liquid nitrogen or “LN2”
cryogenic 43 temperatures; -196 °C) and held continuously at that temperature for some period of time. 44

We further presume that the patient received a “good cryopreservation” with minimal ischemic 45 damage
and adequate cryoprotectant saturation of the tissues, especially of the brain: “Patients stabilized
immediately post-arrest and perfused under good conditions can enter a state of nearly ice free
cryopreservation with very little histological or ultrastructural disruption of the brain.” 46 Patients who
have been “straight-frozen” without any cryoprotectant or who received grossly inadequate local
concentrations of cryoprotectant (Section 7.1.1), 47 or patients who were treated with aldehyde-stabilized
cryopreservation (Section 7.1.5), 48 will require somewhat more intensive nanorobotic procedures for
successful revival.

The chart below shows the level of cryoprotectant saturation actually achieved in the brains of 37 cryonics
patients who were cryopreserved by Alcor 49 during 2000-2020, as directly measured via CT (Computed
Tomography) scan. It appears that over the last 20 years, roughly 38% of Alcor neuro patients have
received between 50%-100% of the CNV (or “concentration necessary to vitrify” the entire brain), while
another 32% of neuros have received 25%-50% of CNV. 50

40
Phaedra C, de Wolf A. Cryonics Protocols at the Cryonics Institute: Research and Practice. Part 3: Cryoprotection. Long
Life 2018 Qtr 2;50(2):13-17; https://immortalistsociety.org/LongLifeV50-02.pdf.
41
https://en.wikipedia.org/wiki/Cryoprotectant.
42
Fahy GM, Wowk B, Wu J, Phan J, Rasch C, Chang A, Zendejas E. Cryopreservation of organs by vitrification: perspectives
and recent advances. Cryobiology. 2004 Apr;48(2):157-78; http://www.21cm.com/pdfs/cryopreservation_advances.pdf.
43
https://en.wikipedia.org/wiki/Cryogenics.
44
https://www.alcor.org/library/alcor-human-cryopreservation-protocol/. See also: “New evidence shows that when human
cryopreservation is carried out under favorable conditions, it causes minimal damage that we can reasonably expect to be
reversible at some time in the future using molecular nanotechnology.” Platt C. Effect of Human Cryopreservation Protocol
on the Ultrastructure of the Canine Brain. CryoCare Report #4, Jul 1995; https://www.alcor.org/library/effect-of-human-
cryopreservation-protocol-on-the-ultrastructure-of-the-canine-brain-platt/.
45
https://en.wikipedia.org/wiki/Ischemia.
46
Darwin M. Cryonics: An Historical Failure Analysis. Part III: Dissociation of Researchers from the Clinical Environment.
2010;
https://web.archive.org/web/20140906234205/http://cryoeuro.eu:8080/download/attachments/425990/Cryonics_Failure_Anal
ysis_Part_3v5.4.pdf.
47
Completely unprotected tissues will experience massive mechanical damage* likely requiring more extensive repairs than
those described here.
*
Lovelock JE, Smith AU. Studies in Golden Hamsters During Cooling To and Rewarming From Body Temperatures Below
0 degrees C. Part III: Biophysical Aspects and General Discussion. Proc R Soc Lond B Biol Sci. 1956 Jul 24;145(920):427-
42; https://www.ncbi.nlm.nih.gov/pubmed/13359396; Fahy GM, Takahashi T, Crane AM. Histological cryoprotection of rat
and rabbit brains. CryoLetters 1984;5:33-46.
48
McIntyre RL, Fahy GM. Aldehyde-stabilized cryopreservation. Cryobiology. 2015 Dec;71(3):448-58;
https://www.sciencedirect.com/science/article/pii/S001122401500245X.
49
Alcor Life Extension Foundation, the leading provider of cryopreservation and long-term cryonics storage services in the
world, as of 2021; https://www.alcor.org/.
50
Benjamin M, de Wolf A. Alcor Case Metrics 2000-2020. Cryonics 2021 Qtr II; 42(2):10-30, chart p. 28;
https://www.alcor.org/docs/cryonics-magazine-2021-02.pdf.
 26

While this book focuses primarily on revival from a “good cryopreservation,” methods are also presented
for reviving patients who may have received poor cryopreservation with minimal or no prevention of ice
formation, possibly including substantial ischemic damage. This is necessary because while the strongest
scientific case for the utility of cryonics today can made by assuming ideal cryopreservation conditions
immediately following legal death by cardiopulmonary criteria, it has long been an ideological practice of
cryonics to cryopreserve people even after very long delays after legal death as an ethical imperative if that
was the wish of the person being cryopreserved. Notes Brian Wowk: 51

“The word ‘cryonics’ is actually a name for two different ideas. The first idea is that human
cryopreservation under ideal conditions today could be reversible in the future. The second idea is
that medicine should never leave patients behind; every patient beyond the capabilities of
contemporary care should be cryopreserved instead of destroyed, even if found in poor condition.
The distinction is necessary because it is possible to agree with the first idea even while not
accepting the second. The first idea is a scientific proposition, while the second is a philosophical
imperative.”

Cryonics patients may have their entire body cryopreserved (i.e., a “whole-body” patient) 52 or may choose
for financial and other reasons to cryopreserve only their head (i.e., a “neuro” patient) 53 or only an isolated
brain. The nanorobotic procedures described in this book are generally presented as being applied to a
whole-body patient, thus avoiding the immediate complications of having to rebuild a new trunk that must

51
Wowk B. Ethics of Non-ideal Cryonics Cases. Cryonics 2006 Qtr 4;27(4):10-12; https://www.alcor.org/library/ethics-of-
non-ideal-cryonics-cases/.
52
O’Neal MB, de Wolf A. The Case for Whole-Body. Cryonics 2014 Feb;35(2):16-21; https://www.alcor.org/library/case-for-
whole-body/.
53
Darwin M. But What Will The Neighbors Think? A Discourse On The History And Rationale Of Neurosuspension.
Cryonics 1988 Oct;9(10):40-55; https://www.alcor.org/library/but-what-will-the-neighbors-think/. Bridge S. The
Neuropreservation Option. Cryonics 1995 Qtr 3;16(3):4-7; https://www.alcor.org/library/neuropreservation-option/. See also:
https://www.alcor.org/library/case-for-neuropreservation/ and https://www.alcor.org/library/neuropreservation-faq/.
 27

be seamlessly attached to the fully-repaired previously-cryopreserved head (Chapter 6). Nevertheless, the
discussion here often focuses on reparative issues specific to the brain since revival processes for the
noncephalic trunk should be technically less challenging and more forgiving of error than for the brain.
This is because the nonbrain portions of the body appear to be less important (though not entirely
unimportant) 54 for preserving the unique memories and personality of the patient, and could in principle be
partially (though inexactly) restored using such prosaic pre-nano technologies as 3D bioprinting, 55
cloning, 56 and conventional surgery. 57

In brief, the revival methods presented in this book involve three stages: (1) collecting information from
preserved structure, (2) computing how to fix damaged structure, and (3) implementing the repair
procedure. The first and last of these stages involve sophisticated robots (“nanorobots”; Section 1.2) small
enough to pass through blood vessels and other tissue vasculature, as well as a temporary nanorobotic
support structure (“vasculoid”; Section 1.2.4) that covers the inside wall of the vessels. The activity in the
second stage is primarily computational and takes place outside of the body using an external high-
performance computer and specialized software.

How long will the revival process take, and what will it cost? There is considerable uncertainty in the
estimates, but it appears that revival may take several months (Table 16) using either of the two revival
approaches proposed in this book – conventional cell repair (“Plan A”; Chapter 4) or molecular
reconstruction (“Plan B”; Chapter 5). The key driver of operating expenses is the price of the energy
required to power the nanorobots and computers, with a total revival cost of ~$2 million (Table 17) for
whole-body patients using Plan A assuming contemporary electricity costs, and similarly using Plan B
assuming future energy costs about 100-fold cheaper than today (Appendix G), to be made possible by
widespread commercial atomically precise manufacturing (Section 1.3). Implementing either Plan requires
considerable development, including designing and building the nanomachines and gaining the biological

54
For example, fingerprints differ between genetic identical twins.* Many physical body features such as muscle mass, bone
density, body shape and height, microbiome, and other physical characteristics that are significantly determined by
environment, parental behaviors, nutrition, exercise patterns, etc. will be unique to a particular individual. See further
discussion in Section 2.1.4.
*
O’Neal MB, de Wolf A. The Case for Whole-Body. Cryonics 2014 Feb;35(2):16-21; https://www.alcor.org/library/case-
for-whole-body/.
55
Mandrycky C, Wang Z, Kim K, Kim DH. 3D bioprinting for engineering complex tissues. Biotechnol Adv. 2016 Jul-
Aug;34(4):422-434; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879088/. Huang Y, Zhang XF, Gao G, Yonezawa T,
Cui X. 3D bioprinting and the current applications in tissue engineering. Biotechnol J. 2017 Aug;12(8);
https://www.ncbi.nlm.nih.gov/pubmed/28675678. Ong CS, Yesantharao P, Huang CY, Mattson G, Boktor J, Fukunishi T,
Zhang H, Hibino N. 3D bioprinting using stem cells. Pediatr Res. 2018 Jan;83(1-2):223-231;
https://www.nature.com/articles/pr2017252.pdf. Francis Collins. Progress Toward 3D Printed Human Organs. NIH Director’s
Blog, 20 Jun 2019; https://directorsblog.nih.gov/2019/06/20/progress-toward-3d-printed-human-organs/. Organ printing;
https://en.wikipedia.org/wiki/Organ_printing. Juliet Childers. How Close are we to 3D Printing Bodies? Edgy, 14 Mar 2018;
https://edgy.app/how-close-3d-printing-bodies. Caroline Haskins. ‘Marie’ Is the First Life-Sized, 3D-Printed Human Body.
Motherboard Tech by Vice, 14 Dec 2018; https://www.vice.com/en_us/article/yw7kzv/marie-is-the-first-life-sized-3d-printed-
human-body.
56
Shawlot W, Behringer RR. Requirement for Lim1 in head-organizer function. Nature. 1995 Mar 30;374(6521):425-30;
https://www.ncbi.nlm.nih.gov/pubmed/7700351 (headless mice cloned). Shewmon DA, Capron AM, Peacock WJ, Schulman
BL. The use of anencephalic infants as organ sources. A critique. JAMA. 1989 Mar 24-31;261(12):1773-81;
https://www.ncbi.nlm.nih.gov/pubmed/2645454. Canadian Paediatric Society. Use of anencephalic newborns as organ
donors. Paediatr Child Health. 2005 Jul;10(6):335-7; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2722973/.
57
Lamba N, Holsgrove D, Broekman ML. The history of head transplantation: a review. Acta Neurochirurgica. 2016
Dec;158(12):2239–2247; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5116034. Furr A, Hardy MA, Barret JP, Barker JH.
Surgical, ethical, and psychosocial considerations in human head transplantation. Int J Surg. 2017 May;41:190-195;
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5490488.
 28

knowledge needed to create the algorithm that determines how to repair the preserved structure. These
research questions are described throughout the text and are collected in Appendix R.

1.1 Scientific Rationale for Human Cryopreservation

Many biological living materials have been preserved for later
use and then restored to full functionality after warming,
including human eggs 58 and sperm, embryos and blastocysts,
stem cells, testicular tissue, cord blood, histological samples,
and plant seeds. 59 Although no whole human or other complex
mammal has yet been cryopreserved to liquid nitrogen
temperatures and then successfully restored to full functionality
at normal body temperature, there have been many
experimental successes in cryonics since the first demonstration
in 1966 of near normal-appearing brainwave activity in a cat
brain that was frozen to -20 °C and then rewarmed. 60 These
successes include the first successful vitrification, transplantation, and long-term survival of a vital
mammalian whole organ (a rabbit kidney; image, above) after cooling to full cryogenic temperatures, 61 the
first demonstration of memory retention in a cryopreserved and revived simple animal, 62 and the first
demonstration of whole brain vitrification with perfect preservation of neural connectivity (aka. the
“connectome”) throughout entire rabbit and pig brains after cooling to cryogenic temperatures. 63
Vitrification is a well-known alternative to cryopreservation by freezing that allows hydrated living cells to
be cooled to cryogenic temperatures in the absence of ice. 64

58
Human embryos have been successfully cryopreserved for up to 24 years. Sabrina Barr, “Longest-frozen embryo is born
after being preserved for 24 years,” The Independent, 20 Dec 2017; https://www.independent.co.uk/life-style/health-and-
families/embryo-24-years-frozen-born-baby-longest-ever-tina-benjamin-gibson-emma-wren-nedc-tennessee-a8119776.html.
59
https://en.wikipedia.org/wiki/Cryopreservation#Freezable_tissues.
60
Suda I, Kito K, Adachi C. Viability of long term frozen cat brain in vitro. Nature. 1966 Oct 15;212(5059):268-70;
https://pubmed.ncbi.nlm.nih.gov/5970120/.
61
Fahy GM, Wowk B, Pagotan R, Chang A, Phan J, Thomson B, Phan L. Physical and biological aspects of renal vitrification.
Organogenesis. 2009 Jul;5(3):167-75; https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20046680/. After the rabbit received
the kidney that had been cryopreserved: “Clinically, the animal regained normal drinking behavior, a normal fecal output
score, and a normal urine volume output score by about 1-2 weeks postoperatively, but food consumption and to a lesser
extent water consumption and urine output declined on balance after day 24. The rabbit lost about 18% of its body weight by
the fifth postoperative day and thereafter maintained this weight....After ensuring that the animal appeared capable of living
indefinitely using the vitrified kidney as the sole renal support, it was euthanized for histological follow-up on day 48.”
Histology revealed some freezing damage in the transplanted organ, which had remained functional nonetheless.
62
Vita-More N, Barranco D. Persistence of Long-Term Memory in Vitrified and Revived Caenorhabditis elegans.
Rejuvenation Res. 2015 Oct;18(5):458-63; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4620520/. The story behind the
research project (illustrated): Vita-More N. Persistence of Long-Term Memory in Vitrified and Revived Simple Animals.
Cryonics 2015 Sep;36(9):6-11; https://www.alcor.org/docs/cryonics-magazine-2015-09.pdf.
63
McIntyre RL, Fahy GM. Aldehyde-stabilized cryopreservation. Cryobiology. 2015 Dec;71(3):448-58;
https://www.sciencedirect.com/science/article/pii/S001122401500245X.
64
Fahy GM, Wowk B. Principles of Ice-Free Cryopreservation by Vitrification. Methods Mol Biol. 2021;2180:27-97;
https://pubmed.ncbi.nlm.nih.gov/32797408/.
 29

The interested reader can peruse the substantial literature describing the scientific rationale for cryonics 65
and popular arguments favoring the practice, 66 which will not be reviewed here. According to an Open
Letter on Cryonics, 67 first signed by 68 scientists in 2004: “Cryonics is a legitimate science-based
endeavor that seeks to preserve human beings, especially the human brain, by the best technology
available. Future technologies for resuscitation can be envisioned that involve molecular repair by
nanomedicine, highly advanced computation, detailed control of cell growth, and tissue regeneration.
With a view toward these developments, there is a credible possibility that cryonics performed under the
best conditions achievable today can preserve sufficient neurological information to permit eventual
restoration of a person to full health.” There is now an emerging scientific consensus on the feasibility of
cryopreserving complex mammalian tissues, 68 and the Society for Cryobiology is no longer openly hostile
to cryonicists, though still eschewing cryonics as part of its professional mission (Appendix A).

A review of the scientific rationale for cryonics by Ben Best in 2008 69 explained that “[v]ery low
temperatures create conditions that can preserve tissue for centuries, possibly including the neurological
basis of the human mind. Through a process called vitrification, brain tissue can be cooled to cryogenic
temperatures without ice formation. Damage associated with this process is theoretically reversible in the
same sense that rejuvenation is theoretically possible by specific foreseeable technology. Injury to the
brain due to stopped blood flow is now known to result from a complex series of processes that take much
longer to run to completion than the 6 minute limit of ordinary resuscitation technology. Reperfusion
beyond the 6 minute limit primarily damages blood vessels rather than brain tissue. Apoptosis of neurons
takes many hours. This creates a window of opportunity between legal death and irretrievable loss of life
for human and animal subjects for cryopreservation with possibility of future resuscitation. Under ideal
conditions, the time interval between onset of clinical death and beginning of cryonics procedures can be
reduced to less than 1 minute, but much longer delays could also be compatible with ultimate survival.
Although the evidence that cryonics may work is indirect, the application of indirect evidence is essential in
many areas of science. If complex changes due to aging are reversible at some future date, then similarly
complex changes due to stopped blood flow and cryopreservation may also be reversible, with life-saving
results for anyone with medical needs that exceed current capabilities.”

65
Feinberg G. Physics and Life Prolongation. Phys Today 1966;19(11):45; https://www.biostasis.com/physics-and-life-
prolongation/. The Cryobiological Case for Cryonics. Cryonics 1988 Mar;9(3):23-36; https://www.alcor.org/library/the-
cryobiological-case-for-cryonics/. Merkle RC. The Technical Feasibility of Cryonics. Med Hypotheses 1992 Sep;39(1):6-16;
http://www.merkle.com/cryo/TheTechnicalFeasibilityOfCryonics.pdf. Lemler J, Harris SB, Platt C, Huffman TM. The arrest
of biological time as a bridge to engineered negligible senescence. Ann N Y Acad Sci. 2004 Jun;1019:559-63;
http://www.alcor.org/Library/pdfs/Lemler-Annals.pdf. Best BP. Scientific justification of cryonics practice. Rejuvenation
Res. 2008 Apr;11(2):493-503; https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18321197/. De Wolf A, Platt C. Human
Cryopreservation Procedures. Alcor Life Extension Foundation, 2020; https://www.alcor.org/library/human-cryopreservation-
procedures/. Scientists’ Cryonics FAQ, 2020; https://www.alcor.org/library/faq-scientists-questions/. See dynamic
bibliography at
https://pubmed.ncbi.nlm.nih.gov/?orig_db=PubMed&cmd=Search&defaultField=Title%20Word&term=cryonics. See also:
https://www.alcor.org/library/#scientific.
66
Urban T. Why Cryonics Makes Sense. Wait But Why, 24 Mar 2016; https://waitbutwhy.com/2016/03/cryonics.html. See
also: https://www.alcor.org/library/faq-general-questions/.
67
https://www.biostasis.com/scientists-open-letter-on-cryonics/.
68
Lewis JK, Bischof JC, Braslavsky I, Brockbank KG, Fahy GM, Fuller BJ, Rabin Y, Tocchio A, Woods EJ, Wowk BG,
Acker JP, Giwa S. The Grand Challenges of Organ Banking: Proceedings from the first global summit on complex tissue
cryopreservation. Cryobiology. 2016 Apr;72(2):169-82; https://www.organpreservationalliance.org/s/Lewis-2016-Organ-
Banking-Summit-proceedings.pdf.
69
Best BP. Scientific justification of cryonics practice. Rejuvenation Res. 2008 Apr;11(2):493-503;
https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18321197/.
 30

Lemler et al. 70 add that “[t]he ultrastructure of the brain can now be excellently preserved by vitrification,
and solutions needed for vitrification can now be distributed through organs with retention of organ
viability after transplantation. Current law requires a few minutes of cardiac arrest before cryopreservation
of terminal patients, but dogs and cats have recovered excellent brain function after 16-60 minutes of
complete cerebral ischemia. The arrest of biological time as a bridge to engineered negligible senescence,
therefore, appears consistent with current scientific and medical knowledge.”

In 2019, a detailed human Medical Biostasis Protocol was published 71 with the intention of showing how
human cryopreservation could be practiced as an elective medical procedure in which the transition
between the decline of a terminal patient and the start of cryonics procedures is managed by medical
professionals (e.g., in a regular hospital setting). The introduction to the document, which resulted from a
collaborative effort between cryobiology researchers and medical professionals, reads as follows:

“Medical biostasis is an experimental procedure that induces metabolic arrest at cryogenic

temperatures to allow terminally ill patients to benefit from future medical advances and restore
them to good health. Practiced as a hospital-based, elective medical procedure, medical biostasis
consists of three distinct procedures: induction of hypothermic circulatory arrest, cryoprotection,
and long-term care at intermediate temperatures (between -120 ℃ and -130 ℃). This document
sets out a detailed protocol for medical biostasis, outlines a variation of this protocol for out-of-
hospital emergency cases, and outlines research directions to further optimize this protocol.”

The Protocol ends with a discussion of the requirements for long-term maintenance of cryopreserved
patients, but does not discuss specific methods of revival. According to the Protocol authors, placing a
patient in medical biostasis at cryogenic temperatures “prevents any kind of critical condition from
advancing and allows science and medicine to catch up to the point where matter can be manipulated at the
molecular level and restoration of the patient to good health is feasible. 72” A few professional
organizations are starting to take notice. For instance, EMRA (the Emergency Medicine Residents’
Association) recently added a webpage 73 advising hospital staff how to observe proper procedures when
confronted with cryonics patients.

To fully understand the technical basis for future revival from medical biostasis using nanotechnology, we
must start with a brief description of the nascent field of medical nanorobotics.

1.2 Medical Nanorobotics

The early genesis of the concept of medical nanorobots, manufactured in nanofactories, sprang from the
visionary idea that tiny nanomachines could be designed, manufactured, and introduced into the human

70
Lemler J, Harris SB, Platt C, Huffman TM. The arrest of biological time as a bridge to engineered negligible senescence.
Ann N Y Acad Sci. 2004 Jun;1019:559-63; http://www.alcor.org/Library/pdfs/Lemler-Annals.pdf.
71
De Wolf A, Salmensuu V. Medical Biostasis Protocol (V 1.0); https://www.biostasis.com/protocol.pdf. Described in: de
Grey ADNJ. Cryonics Takes Another Big Step Toward the Mainstream. Rejuvenation Res. 2020 Jun 16;23(3):191-2;
https://www.liebertpub.com/doi/full/10.1089/rej.2020.2356.
72
Robert A. Freitas Jr., “Chapter 23. Comprehensive Nanorobotic Control of Human Morbidity and Aging,” in Gregory M.
Fahy, Michael D. West, L. Stephen Coles, and Steven B. Harris, eds, The Future of Aging: Pathways to Human Life
Extension, Springer, New York, 2010, pp. 685-805; http://www.nanomedicine.com/Papers/Aging.pdf.
73
Zald Altawil, MD, “A Different Kind of Therapeutic Hypothermia,” EMRA/Clinical, 15 Dec 2018;
https://www.emra.org/emresident/article/cryonics/.
 31

body to perform cellular repairs at the molecular level. Although the medical application of
nanotechnology was championed in the popular writings of Drexler 74 in the 1980s and 1990s and in the
technical writings of Freitas 75 in the 1990s, 2000s, and 2010s, the first scientist to voice the possibility was
the late Nobel physicist Richard P. Feynman, who worked on the Manhattan Project at Los Alamos during
World War II and later taught at Caltech for most of his professorial career.

In his prescient 1959 talk “There’s Plenty of Room at the Bottom,” Feynman proposed employing machine
tools to make smaller machine tools, these to be used in turn to make still smaller machine tools, and so on
all the way down to the atomic level. 76 He prophetically concluded that this is “a development which I
think cannot be avoided.” After discussing his ideas with a colleague, Feynman offered the first known
proposal for a medical nanorobotic procedure of any kind – in this instance, to cure heart disease: “A
friend of mine (Albert R. Hibbs) suggests a very interesting possibility for relatively small machines. He
says that, although it is a very wild idea, it would be interesting in surgery if you could swallow the
surgeon. You put the mechanical surgeon inside the blood vessel and it goes into the heart and looks
around. (Of course the information has to be fed out.) It finds out which valve is the faulty one and takes a
little knife and slices it out. Other small machines might be permanently incorporated in the body to assist
some inadequately functioning organ.” Later in his historic 1959 lecture, Feynman urges us to consider the
possibility, in connection with microscopic biological cells, “that we can manufacture an object that
maneuvers at that level!” The field had progressed far enough by 2007, half a century after Feynman’s
speculations, to allow Martin Moskovits, Professor of Chemistry and Dean of Physical Science at UC Santa
Barbara, to write 77 that “the notion of an ultra-small robot that can, for example, navigate the bloodstream
performing microsurgery or activating neurons so as to restore muscular activity, is not an unreasonable
goal, and one that may be realized in the near future.”

Many questions arise when one first encounters the idea of micron-scale nanorobots, constructed of
nanoscale components and operating inside the human body. At the most fundamental level, technical
questions about the influence of quantum effects on molecular structures, friction and wear among
nanomechanical components, radiation damage, other failure mechanisms, the influence of thermal noise
on reliability, and the effects of Brownian bombardment on nanomachines have all been extensively
discussed and resolved in the literature. 78 Self-assembled molecular motors consisting of just 50-100 atoms

74
Drexler KE. Engines of Creation: The Coming Era of Nanotechnology. Anchor Press/Doubleday, New York, 1986, Chapter
7 “Engines of Healing”; https://web.archive.org/web/20180722191948/http://e-
drexler.com/d/06/00/EOC/EOC_Chapter_7.html. Drexler KE, Peterson C, Pergamit G. Unbounding the Future: The
Nanotechnology Revolution. William Morrow/Quill Books, New York, 1991, Chapter 10 “Nanomedicine”;
https://web.archive.org/web/20100302193412/http://www.foresight.org/UTF/Unbound_LBW/chapt_10.html.
75
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999;
http://www.nanomedicine.com/NMI.htm. Freitas RA Jr. Nanomedicine, Volume IIA: Biocompatibility. Landes Bioscience,
Georgetown, TX, 2003; http://www.nanomedicine.com/NMIIA.htm. Freitas RA Jr. “Technical Analyses of Types of
Diamondoid Medical Nanorobots,” http://www.nanomedicine.com/#NanorobotAnalyses.
76
Feynman RP. There’s plenty of room at the bottom. Eng Sci (CalTech) 1960;23:22-36;
http://www.zyvex.com/nanotech/feynman.html.
77
Moskovits M. Nanoassemblers: A likely threat? Nanotech. Law & Bus. 2007;4:187-195; https://heinonline.org/hol-cgi-
bin/get_pdf.cgi?handle=hein.journals/nantechlb4&section=29.
78
Drexler KE. Nanosystems: Molecular Machinery, Manufacturing, and Computation. John Wiley & Sons, New York, 1992;
https://www.amazon.com/dp/0471575186/. Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience,
Georgetown, TX, 1999; http://www.nanomedicine.com/NMI/2.1.htm.
 32

have been demonstrated experimentally since the late 1990s. 79 Published discussions of technical issues of
specific relevance to medical nanorobots include proposed methods for recognizing, sorting and pumping
individual molecules; 80 theoretical designs for mechanical nanorobot sensors; 81 flexible nanorobot hull
surfaces, 82 power sources, 83 communications 84 and navigation 85 systems, and manipulator mechanisms; 86
nanorobot mobility mechanisms for travel through bloodstream, tissues and cells, 87 and for penetration of
the blood-brain barrier; 88 onboard clocks 89 and nanocomputers; 90 and the full panoply of nanorobot
biocompatibility issues. 91

79
Kelly TR, De Silva H, Silva RA. Unidirectional rotary motion in a molecular system. Nature. 1999 Sep 9;401:150-152;
https://ww.bostoncollege.org/content/dam/bc1/schools/mcas/Chemistry/news-and-notes/pdf/3.pdf. Koumura N, Zijlstra RW,
van Delden RA, Harada N, Feringa BL. Light-driven monodirectional molecular rotor. Nature 1999 Sep 9;401:152-155;
https://core.ac.uk/download/pdf/148148838.pdf. Huang TJ, Lu W, Tseng HR, et al. Molecular shuttle switching in closely
packed Langmuir films, 11th Foresight Conf. Mol. Nanotech., San Francisco CA, 10-12 Oct 2003. Leigh DA, Wong JKY,
Dehez F, Zerbetto F. Unidirectional rotation in a mechanically interlocked molecular rotor. Nature. 2003 Jul
10;424(6945):174-179; http://biotheory.phys.cwru.edu/phys414/nature01758.pdf. Browne WR, Feringa BL. Making
molecular machines work. Nat Nanotechnol. 2006 Oct;1(1):25-35;
https://www.rug.nl/research/portal/files/6702682/2006NatureNanotechBrowne.pdf. Kay ER, Leigh DA, Zerbetto F. Synthetic
molecular motors and mechanical machines. Angew Chem Int Ed 2007;46(1-2):72-191;
https://pubmed.ncbi.nlm.nih.gov/17133632/.
80
Drexler KE. Nanosystems: Molecular Machinery, Manufacturing, and Computation. John Wiley & Sons, New York, 1992,
Section 13.2; https://www.amazon.com/dp/0471575186/. Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes
Bioscience, Georgetown, TX, 1999, Chapter 3, “Molecular Transport and Sortation”;
http://www.nanomedicine.com/NMI/3.1.htm.
81
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999, Chapter 4,
“Nanosensors and Nanoscale Sensing”; http://www.nanomedicine.com/NMI/4.1.htm.
82
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999, Chapter 5, “Shapes
and Metamorphic Surfaces”; http://www.nanomedicine.com/NMI/5.1.htm. Hogg T. Energy dissipation by metamorphic
micro-robots in viscous fluids. J Micro-Bio Robotics 2016; 11(1-4):85-95; https://arxiv.org/pdf/1507.01145.
83
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999, Chapter 6,
“Power”; http://www.nanomedicine.com/NMI/6.1.htm. Hogg T, Freitas RA Jr. Chemical power for microscopic robots in
capillaries. Nanomedicine. 2010 Apr;6(2):298-317; https://arxiv.org/pdf/0906.5022.
84
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999, Chapter 7,
“Communication”; http://www.nanomedicine.com/NMI/7.1.htm. Hogg T, Freitas RA Jr. Acoustic communication for
medical nanorobots. Nano Commun Networks 2012; 3(2):83-102; https://arxiv.org/pdf/1202.0568.
85
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999, Chapter 8,
“Navigation”; http://www.nanomedicine.com/NMI/8.1.htm.
86
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999, Section 9.3,
“Nanomanipulators”; http://www.nanomedicine.com/NMI/9.3.htm.
87
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999, Section 9.4, “In
Vivo Locomotion”; http://www.nanomedicine.com/NMI/9.4.htm. Hogg T. Using surface-motions for locomotion of
microscopic robots in viscous fluids. J Micro-Bio Robotics. 2014; 9(3-4):61-77; https://arxiv.org/pdf/1311.0801.
88
Freitas RA Jr. The Alzheimer Protocols: A Nanorobotic Cure for Alzheimer’s Disease and Related Neurodegenerative
Conditions. IMM Report No. 48, June 2016, 433 pp; Section 4.3 “Medical Nanorobots: Ingress to, and Egress from, the
Brain”; http://www.imm.org/Reports/rep048.pdf. Freitas RA Jr. Nanomedicine, Volume IIA: Biocompatibility. Landes
Bioscience, Georgetown, TX, 2003, Section 15.3.6.5, “Biocompatibility with Neural Cells”;
http://www.nanomedicine.com/NMIIA/15.3.6.5.htm#p8.
89
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999, Section 10.1,
“Nanochronometry”; http://www.nanomedicine.com/NMI/10.1.htm.
 33

The idea of placing semi-autonomous self-powered nanorobots inside of us might seem a bit odd, but the
human body already teems with similar natural nanodevices. More than 40 trillion single-celled microbes
swim through our colon, outnumbering our tissue cells almost ten to one. 92 Many bacteria move by
whipping around a tiny tail, or flagellum, that is driven by a 30-nanometer biological ionic nanomotor
powered by pH differences between the inside and the outside of the bacterium. Our bodies also maintain a
population of more than a trillion motile biological nanodevices called fibroblasts and white cells such as
neutrophils and lymphocytes, each measuring up to ~10 μm in size. 93 These beneficial natural nanorobots
are constantly crawling around inside us, repairing damaged tissues, attacking invading microbes, and
gathering up foreign particles and transporting them to various organs for disposal from the body. 94

The greatest power of nanomedicine will emerge as we learn to design and construct complete artificial
nanorobots using nanometer-scale parts and subsystems such as diamondoid bearings and gears,
nanomotors and molecular pumps, nanomanipulators, nanosensors, nanobatteries, and nanocomputers.

In the subsections below, we briefly describe four major classes of hypothetical medical nanorobots, listed
in order of increasing capacity and sophistication:

(1) free-floating nonmotile nanorobots (e.g., respirocytes; Section 1.2.1),

(2) motile nanorobots (e.g., microbivores; Section 1.2.2),

(3) cell repair nanorobots (e.g., chromallocytes; Section 1.2.3), and

(4) multidevice nanorobotic systems (e.g., vasculoid; Section 1.2.4).

We then enumerate some of the major advantages of nanorobots over other medical approaches and
instrumentalities (Section 1.2.5).

Much of the following material in Section 1.2 is drawn from a previously published summary. 95

90
Drexler KE. Nanosystems: Molecular Machinery, Manufacturing, and Computation. John Wiley & Sons, New York, 1992,
Chapter 12; https://www.amazon.com/dp/0471575186/. Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes
Bioscience, Georgetown, TX, 1999, Section 10.2, “Nanocomputers”; http://www.nanomedicine.com/NMI/10.2.htm.
91
Freitas RA Jr. Nanomedicine, Volume IIA: Biocompatibility. Landes Bioscience, Georgetown, TX, 2003;
http://www.nanomedicine.com/NMIIA.htm.
92
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999, Section 8.5.1,
“Cytometrics”; http://www.nanomedicine.com/NMI/8.5.1.htm.
93
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999, Section 8.5.1,
“Cytometrics”; http://www.nanomedicine.com/NMI/8.5.1.htm.
94
Freitas RA Jr. Nanomedicine, Volume IIA: Biocompatibility. Landes Bioscience, Georgetown, TX, 2003, Section 15.4.3.1,
“Phagocytes, Phagocytosis, and the RES”; http://www.nanomedicine.com/NMIIA/15.4.3.1.htm.
95
Freitas RA Jr. The Alzheimer Protocols: A Nanorobotic Cure for Alzheimer’s Disease and Related Neurodegenerative
Conditions. IMM Report No. 48, June 2016, 433 pp; Section 4.2 “Medical Nanorobots: Background”;
http://www.imm.org/Reports/rep048.pdf.
 34

1.2.1 Respirocyte-Class Nanorobots

The first theoretical design study of a medical nanorobot ever published in a peer-reviewed medical journal
(by Freitas in 1998) 96 described an artificial mechanical red blood cell or “respirocyte” to be made of 18
billion precisely arranged atoms. The device was to be a
bloodborne spherical 1-μm diameter diamondoid 1000-
atmosphere pressure vessel 97 with active pumping 98
powered by the oxidation of endogenous serum
glucose, 99 able to deliver 236 times more oxygen to the
tissues per unit volume than natural red cells and to
manage acidity caused by carbonic acid formation, all
controlled by gas concentration sensors 100 and an onboard
nanocomputer. 101 The basic operation of respirocytes
(image, left; artwork by Forrest Bishop) 102 is
straightforward. These nanorobots would mimic the
action of the natural hemoglobin(Hb)-filled red blood
cells, while operating at 1000 atm vs. only 0.1-0.5 atm
equivalent for natural Hb. In the tissues, oxygen will be
pumped out of the device by the molecular sorting rotors (Section 4.10.1) on one side. Carbon dioxide will
be pumped into the device by molecular sorting rotors on the other side, one molecule at a time. Half a
minute later, when the respirocyte reaches the patient’s lungs in the normal course of the circulation of the
blood, these same rotors reverse their direction of rotation, recharging the device with fresh oxygen and
dumping the stored CO 2 , which diffuses into the lungs and can then be exhaled by the patient. Each rotor
requires very little power, only ~0.03 pW to pump ~106 molecules/sec in continuous operation.

96
Freitas RA Jr. Exploratory design in medical nanotechnology: a mechanical artificial red cell. Artif Cells Blood Substit
Immobil Biotechnol. 1998 Jul;26(4):411-30; https://www.tandfonline.com/doi/pdf/10.3109/10731199809117682. A longer
version of this paper appears at:
https://web.archive.org/web/20100420085137/http://www.foresight.org/Nanomedicine/Respirocytes.html.
97
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999, Section 10.3,
“Pressure Storage and Ballasting”; http://www.nanomedicine.com/NMI/10.3.htm.
98
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999, Section 3.4.2,
“Sorting Rotors”; http://www.nanomedicine.com/NMI/3.4.2.htm.
99
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999, Section 6.3.4,
“Chemical Energy Conversion Processes”; http://www.nanomedicine.com/NMI/6.3.4.htm.
100
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999, Section 4.2.1,
“Broadband Receptor Arrays”; http://www.nanomedicine.com/NMI/4.2.1.htm.
101
Drexler KE. Nanosystems: Molecular Machinery, Manufacturing, and Computation. John Wiley & Sons, New York, 1992,
Chapter 12; https://www.amazon.com/dp/0471575186/. Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes
Bioscience, Georgetown, TX, 1999, Section 10.2, “Nanocomputers”; http://www.nanomedicine.com/NMI/10.2.htm.
102
https://web.archive.org/web/20160325053612/https://foresight.org/Nanomedicine/Gallery/Captions/Image139.html.
 35

In the exemplar respirocyte

design, 103 onboard pressure
tanks can hold up to 3
billion oxygen (O 2 ) or
carbon dioxide (CO 2 )
molecules. Molecular
sorting rotors 104 are
arranged on the surface to
load and unload gases from
the pressurized tanks. Tens
of thousands of these
individual pumps cover a
large fraction of the hull
surface of the respirocyte. Molecules of oxygen or carbon
dioxide may drift into their respective binding sites on the
exterior rotor surface and be carried into the respirocyte interior
as the rotor turns in its casing. The sorting rotor array is
organized into 12 identical pumping stations (image, above
right) laid out around the equator of the respirocyte (cutaway
image, at right), with oxygen rotors on the left, carbon dioxide
rotors on the right, and water rotors in the middle of each
station, with tenfold redundancy in all components for
enhanced reliability. Temperature 105 and concentration 106
sensors tell the devices when to release or pick up gases. Each
pumping station will have special pressure sensors 107 to receive
ultrasonic acoustic messages 108 so the physician can (a) tell the
devices to turn on or off, or (b) change the operating parameters
of the devices, while the nanorobots are inside a patient. The
onboard nanocomputer enables complex device behaviors also
remotely reprogrammable by the physician via externally
applied ultrasound acoustic signals. Internal power will be transmitted mechanically or hydraulically using
an appropriate working fluid, and can be distributed as required using rods and gear trains 109 or using pipes

103
Freitas RA Jr. Exploratory design in medical nanotechnology: a mechanical artificial red cell. Artif Cells Blood Substit
Immobil Biotechnol. 1998 Jul;26(4):411-30; https://www.tandfonline.com/doi/pdf/10.3109/10731199809117682. A longer
version of this paper appears at:
https://web.archive.org/web/20100420085137/http://www.foresight.org/Nanomedicine/Respirocytes.html.
104
Drexler KE. Nanosystems: Molecular Machinery, Manufacturing, and Computation. John Wiley & Sons, New York, 1992,
Section 13.2; https://www.amazon.com/dp/0471575186/. Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes
Bioscience, Georgetown, TX, 1999, Section 3.4.2, “Sorting Rotors”; http://www.nanomedicine.com/NMI/3.4.2.htm.
105
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999, Section 4.6,
“Thermal Nanosensors”; http://www.nanomedicine.com/NMI/4.6.htm.
106
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999, Section 4.2,
“Chemical and Molecular Nanosensors”; http://www.nanomedicine.com/NMI/4.2.htm.
107
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999, Section 4.5,
“Pressure Sensing”; http://www.nanomedicine.com/NMI/4.5.htm.
108
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999, Section 7.2.2,
“Acoustic Broadcast Communication”; http://www.nanomedicine.com/NMI/7.2.2.htm.
109
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999, Section 6.4.3.4,
“Gear Trains and Mechanical Tethers”; http://www.nanomedicine.com/NMI/6.4.3.4.htm.
 36

and mechanically operated valves, controlled by the nanocomputer. There is also a large internal void
surrounding the nanocomputer which can be a vacuum, or can be filled with (or emptied of) up to 6 billion
molecules of water. This will allow the device to control its buoyancy very precisely and provides a crude
but simple method for removing respirocytes from the body using a blood centrifuge (Appendix M), a
future procedure now termed “nanapheresis”. 110

A 5 cc therapeutic dose of 50% respirocyte saline suspension containing 5 trillion nanorobots would
exactly replace the gas carrying capacity of the patient’s entire 5.4 liters of blood. Each device stores
enough onboard glucose/O 2 to provide power for at least one circulation time (60 sec), and can also store
the CO 2 . 111 If up to 1 liter of respirocyte suspension could safely be added to the human bloodstream, 112
this would keep a patient’s tissues oxygenated for up to an hour even if a heart attack caused the heart to
stop beating, or if there was a complete absence of respiration or no
external availability of oxygen. Primary medical applications of
respirocytes might include emergency revival of victims of carbon
monoxide suffocation at the scene of a fire, rescue of drowning victims,
and transfusable pre-oxygenated blood substitution. Respirocytes
(image, left; artwork by Forrest Bishop) 113 could serve as “instant
blood” at an accident scene with no need for blood typing, and, thanks to
the dramatically higher gas-transport efficiency of respirocytes over
natural red cells, a mere 1 cm3 infusion of the devices would provide the
oxygen-carrying ability of a full liter of ordinary blood, possibly saving
lives even in cases of moderate hypovolemia (lost blood fluid volume) that might otherwise lead to
hemorrhagic shock. 114

Larger doses of respirocytes could also: (1) be used as a temporary treatment for anemia and various lung
and perinatal/neonatal disorders, (2) enhance tumor therapies and diagnostics and improve outcomes for
cardiovascular, neurovascular, or other surgical procedures, (3) help prevent asphyxia and permit artificial
breathing (e.g., underwater, high altitude, etc.), and (4) have many additional applications in sports,
veterinary medicine, military science, and space exploration.

110
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999, Section 10.3.6,
“Buoyancy Control and Nanapheresis”; http://www.nanomedicine.com/NMI/10.3.6.htm.
111
Aqueous conversion of CO2 to carbonic acid is slow, a significant fraction of a second, while the reverse takes ~300 nsec at
neutral pH, hence this equilibrium reaction shouldn’t interfere with the respirocyte sorting rotor CO2 molecule identification
and removal process from plasma water. Personal communication from Brian Wowk to Robert Freitas, 30 Sep 2021.
112
Freitas RA Jr. Nanomedicine Vol. IIA: Biocompatibility. Landes Bioscience, Georgetown, TX, 2003, Section 15.6.2,
“Bloodstream Intrusiveness”; http://www.nanomedicine.com/NMI/15.6.2.htm.
113
https://web.archive.org/web/20210508220644/https://foresight.org/Nanomedicine/Gallery/Captions/Image140.html.
114
Takasu A, Prueckner S, Tisherman SA, Stezoski SW, Stezoski J, Safar P. Effects of increased oxygen breathing in a
volume controlled hemorrhagic shock outcome model in rats. Resuscitation. 2000 Aug 1;45(3):209-20;
https://www.sciencedirect.com/science/article/abs/pii/S0300957200001830. Dyson A, Stidwill R, Taylor V, Singer M. The
impact of inspired oxygen concentration on tissue oxygenation during progressive haemorrhage. Intensive Care Med. 2009
Oct;35(10):1783-91; https://pubmed.ncbi.nlm.nih.gov/19618165/.
 37

1.2.2 Microbivore-Class Nanorobots

Perhaps the most widely recognized form of disease is an attack on the
human body by invading viruses, bacteria, protozoa, or other microscopic
parasites. One general class of medical nanorobot could serve as the first-line
nanomedical treatment for pathogen-related disease. Called a “microbivore”,
this artificial nanorobotic white cell substitute, made of diamond and
sapphire, would seek out and harmlessly digest unwanted bloodborne
pathogens. 115 One main task of natural white cells is to phagocytose and kill
microbial invaders in the bloodstream. Microbivore nanorobots would also
perform the equivalent of phagocytosis and microbial killing, but would operate much faster, more reliably,
and under human control.

The baseline microbivore (image, left; hull design

image, above; all microbivore artwork by Forrest
Bishop) 116 is designed as an oblate spheroidal
nanomedical device measuring 3.4 μm in diameter along
its major axis and 2.0 μm in diameter along its minor
axis, consisting of 610 billion precisely arranged
structural atoms in a gross geometric volume of 12.1 μm3
and a dry mass of 12.2 picograms. This size helps to
ensure that the nanorobot can safely pass through or
avoid even the narrowest of human capillaries and other
tight spots in the spleen (e.g., the interendothelial
splenofenestral slits) 117 and elsewhere in the human
118
body, given device motility. The microbivore has a mouth with an irising door, called the ingestion port,
where microbes are fed in to be digested. This port is large enough to internalize a single microbe from
virtually any major bacteremic species in a single gulp. The microbivore also has a rear end, or exhaust
port, where the completely digested remains of the pathogen are harmlessly expelled from the device. The
rear door opens between the main body of the microbivore and a tail-cone structure. According to the
scaling study by Freitas, 119 the device may consume up to 200 pW of continuous power (using bloodstream
glucose and oxygen for energy) while completely digesting trapped microbes at a maximum throughput of
2 μm3 of organic material per 30-second cycle. This “digest and discharge” protocol 120 is conceptually

115
Freitas RA Jr. Microbivores: Artificial mechanical phagocytes using digest and discharge protocol. J Evol Technol
2005;14:1-52; http://www.jetpress.org/volume14/freitas.html.
116
https://web.archive.org/web/20160827082558/https://foresight.org/Nanomedicine/Gallery/Captions/Image197.html.
117
Freitas RA Jr. Nanomedicine Vol. IIA: Biocompatibility. Landes Bioscience, Georgetown, TX, 2003, Section 15.4.2.3,
“Geometrical Trapping in Spleen Vasculature”; http://www.nanomedicine.com/NMI/15.4.2.3.htm.
118
Freitas RA Jr. Nanomedicine Vol. IIA: Biocompatibility. Landes Bioscience, Georgetown, TX, 2003, Section 15.4.2,
“Geometrical Trapping of Bloodborne Medical Nanorobots”; http://www.nanomedicine.com/NMI/15.4.2.htm.
119
Freitas RA Jr. Microbivores: Artificial mechanical phagocytes using digest and discharge protocol. J Evol Technol
2005;14:1-52; http://www.jetpress.org/volume14/freitas.html.
120
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999, Section 10.4.2.4.2,
“Digest and Discharge (DD)”; http://www.nanomedicine.com/NMI/10.4.2.4.2.htm.
 38

similar to the internalization and digestion process practiced by natural phagocytes, except that the artificial
process should be a hundred-fold faster and also cleaner. For example, it is well-known that macrophages
release biologically active compounds during bacteriophagy, 121 whereas well-designed microbivores need
only release biologically inactive effluent.

The first task for the bloodborne microbivore is to

reliably acquire a pathogen to be digested. If the
correct bacterium bumps into the nanorobot surface,
reversible species-specific binding sites on the
microbivore hull can recognize and weakly bind to
the bacterium. A set of 9 distinct antigenic markers
should be specific enough, 122 since all 9 must register
a positive binding event to confirm that a targeted
microbe has been caught. There are 20,000 copies of
these 9-marker receptor sets, distributed in 275 disk-
shaped regions across the microbivore surface (image,
right). Inside each receptor ring are more rotors to
absorb ambient glucose and oxygen from the
bloodstream to provide nanorobot power.

At the center of each 150-nm diameter receptor disk is a grapple silo

(image, left). Once a bacterium has been captured by the reversible
receptors, telescoping robotic grapples 123 rise up out of the microbivore
surface and attach to the trapped bacterium, establishing secure
anchorage to the microbe’s cell wall, capsid, or plasma membrane. The
microbivore grapple arms are about 100 nanometers long and have
various rotating and telescoping joints that allow them to change their
position, angle, and length. After rising
out of its silo, a grapple arm could
execute complex twisting motions (image, right), and adjacent grapple arms
can physically reach each other, allowing them to hand off bound objects as
small as a virus particle. Grapple handoff motions could transport a large
rod-shaped bacterium from its original capture site forward to the ingestion
port at the front of the device. The captive organism would be rotated into
the proper orientation as it approaches the open microbivore mouth. There
the pathogen is internalized into a 2 μm3 morcellation chamber under continuous control of mouth grapples
and an internal mooring mechanism.

There are two concentric cylinders inside the microbivore. The bacterium will be minced into nanoscale
pieces in the morcellation chamber (the smaller inner cylinder), 124 then the remains are pistoned into a

121
Fincher EF 4th, Johannsen L, Kapás L, Takahashi S, Krueger JM. Microglia digest Staphylococcus aureus into low
molecular weight biologically active compounds. Am J Physiol. 1996 Jul;271(1 Pt 2):R149-56;
http://www.ncbi.nlm.nih.gov/pubmed/8760216.
122
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999, Section 8.5.2.2,
“Identification of Cell Type”; http://www.nanomedicine.com/NMI/8.5.2.2.htm.
123
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999, Section 9.3.1.4,
“Telescoping Manipulators”; http://www.nanomedicine.com/NMI/9.3.1.4.htm.
124
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999, Section 9.3.5.1,
“Morcellation and Mincing”; http://www.nanomedicine.com/NMI/9.3.5.1.htm.
 39

separate 2 μm3 digestion chamber (the larger outer cylinder). In a preprogrammed sequence, ~40 different
engineered digestive enzymes will be successively injected and extracted six times during a single
digestion cycle, progressively reducing the morcellate to amino acids, mononucleotides, glycerol, free fatty
acids and simple sugars, using an appropriate array of molecular sorting rotors. These basic end-product
molecules are then harmlessly discharged back into the bloodstream through the exhaust port at the rear of
the device, completing the 30-second digestion cycle (images, below; artwork by Forrest Bishop). When
treatment is finished, the doctor may transmit an ultrasound signal to tell the circulating microbivores that
their work is done. These motile nanorobots may then exit the body through the kidneys by various
means 125 and be excreted with the urine in due course.

A human neutrophil, the most common type of leukocyte or white cell, can capture and engulf a microbe in
a minute or less (images, below), but complete digestion and excretion of the organism’s remains can take
an hour or longer. Our natural white cells – even when aided by antibiotics – can sometimes take weeks or
months to completely clear bacteria from the bloodstream. By comparison, a single terabot (1012-
nanorobot) dose of microbivores should be able to fully eliminate bloodborne pathogens in just minutes, or
hours in the case of locally dense infections.
This is accomplished without increasing the
risk of sepsis or septic shock because all
bacterial components (including all cell-wall
lipopolysaccharide) will be internalized and
fully digested into harmless non-antigenic
molecules prior to discharge from the
microbivore device.

And no matter that a bacterium has acquired multiple drug resistance to antibiotics or to any other
traditional treatment – the microbivore will eat it anyway. Microbivores would be up to ~1000 times
faster-acting than antibiotic-based cures which often need weeks or months to work. The nanorobots
would digest ~100 times more microbial material than an equal volume of natural white cells could digest
in any given time period, and would have far greater maximum lifetime capacity for phagocytosis than
natural white blood cells.

125
Weatherbee C, Freitas RA Jr. Nanoscale robot navigation of the human kidney. In preparation.
 40

1.2.3 Chromallocyte-Class Nanorobots

The chromallocyte 126 is a mobile cell-repair nanorobot whose primary function is to perform chromosome
replacement therapy (CRT). In CRT, the entire chromatin content of the nucleus in a living cell is
extracted and promptly replaced with a new set of prefabricated chromosomes that have been artificially
manufactured as defect-free copies of the originals.

The chromallocyte (images, left; artwork by

Stimulacra) will be capable of limited vascular
surface travel into the capillary bed of the
targeted tissue or organ, followed by
diapedesis (exiting a blood vessel into the
tissues), 127 histonatation (locomotion through
tissues), 128 cytopenetration (entry into the cell
interior; see nanorobot images, below, by E-
spaces), 129 and complete chromatin
replacement in the nucleus of the target cell. The CRT mission ends with a return to the vasculature and
subsequent extraction of the nanodevices from the body at the original infusion site.

This ~3 hour chromosome replacement process is

expected to involve a 26-step sequence of distinct
semi-autonomous sensor-driven activities which
are described at length in a comprehensive
published technical paper on the subject by
Freitas 130 and in summary below, including: (1)
injection, (2) extravasation, (3) ECM immigration,
(4) cytopenetration (image, right), (5) inhibition of
mechanotransduction (to avoid nanorobot
mechanical actions triggering unwanted cell
responses), (6) nuclear localization, (7)
nucleopenetration, (8) blockade of apoptosis (to prevent misinterpretation of CRT processes as damage
demanding cell suicide), (9) arrest of DNA repair (to prevent misinterpretation of CRT processes as
damage demanding repair), (10) blockade of inflammatory signals, (11) deactivation of transcription, (12)
detachment of chromatin from inner nuclear wall lamins (cortex proteins), (13) extension of the
“Proboscis” into the cell nucleus (image below, left), (14) rotation of the Proboscis, (15) deployment of the

126
Freitas RA Jr. The ideal gene delivery vector: Chromallocytes, cell repair nanorobots for chromosome replacement
therapy. J Evol Technol 2007;16:1-97; http://jetpress.org/v16/freitas.pdf.
127
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999, Section 9.4.4.1,
“Nanorobot Diapedesis”; http://www.nanomedicine.com/NMI/9.4.4.1.htm.
128
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999, Section 9.4.4,
“Histonatation”; http://www.nanomedicine.com/NMI/9.4.4.htm.
129
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999, Section 9.4.5,
“Cytopenetration”; http://www.nanomedicine.com/NMI/9.4.5.htm.
130
Freitas RA Jr. The ideal gene delivery vector: Chromallocytes, cell repair nanorobots for chromosome replacement
therapy. J Evol Technol 2007;16:1-97; http://jetpress.org/v16/freitas.pdf.
 41

chromosomal collection funnel, (16) digestion of

stray chromatin, (17) dispensation of new chromatin,
(18) decondensation of the new chromatin, (19) re-
anchoring of the dispensed chromatin to inner
nuclear wall lamins, (20) reactivation of
transcription, (21) reactivation of DNA repair and
other DNA-related maintenance and usage
processes, (22) nuclear emigration, (23) cellular
emigration, (24) ECM emigration, (25) return to
original point of entry into the body, and (26)
removal from the body. Treatment of an entire large
human organ such as a liver, involving simultaneous
CRT on all 250 billion hepatic tissue cells, might require the localized infusion of a ~1 terabot (1012
devices) or ~69 cm3 chromallocyte dose in a 1-liter (7% v/v nanorobots) saline suspension during a ~7 hour
course of therapy. This nanodevice population draws 100-200 watts which lies within estimated nanorobot
thermogenic limits consistent with maintenance of constant human body temperature. 131

Replacement chromosome sets would be manufactured 132 in a

desktop ex vivo chromosome sequencing and manufacturing facility
(conceptual image, right; Section D.1.2), 133 then loaded into the
nanorobots for delivery to specific targeted cells during CRT. The
new DNA is manufactured to incorporate proper methylation for the
target cell type and other post-translational modifications
constituting the “histone code” used by the cell to encode various
chromatin conformations and gene expression states. 134

A single fully-loaded lozenge-shaped 69 μm3 chromallocyte can

measure 4.18 μm and 3.28 μm along cross-sectional diameters and
5.05 μm in length, typically consuming 50-200 pW of power in normal
operation and a maximum of 1000 pW in bursts during outmessaging,
the most energy-intensive task. Onboard power can be provided
acoustically from the outside in an operating-table scenario (image, left)
in which the patient is well-coupled to a medically-safe 1000 W/m2 0.5
MHz ultrasound transverse-plane-wave transmitter throughout the
procedure. The American Institute of Ultrasound in Medicine (AIUM)
deems 10,000-sec exposures to 1000 W/m2 ultrasound to be safe. 135

131
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999, Section 6.5.2,
“Thermogenic Limits in vivo”; http://www.nanomedicine.com/NMI/6.5.2.htm. Freitas RA Jr. The ideal gene delivery vector:
Chromallocytes, cell repair nanorobots for chromosome replacement therapy. J Evol Technol 2007;16:1-97, Section 3.6;
http://jetpress.org/v16/freitas.pdf.
132
Strickland E. DNA manufacturing enters the age of mass production. IEEE Spectrum, 23 Dec 2015;
http://spectrum.ieee.org/biomedical/devices/dna-manufacturing-enters-the-age-of-mass-production.
133
Freitas RA Jr. The ideal gene delivery vector: Chromallocytes, cell repair nanorobots for chromosome replacement
therapy. J Evol Technol 2007;16:1-97, Section 4; http://jetpress.org/v16/freitas.pdf.
134
Villar-Garea A, Imhof A. The analysis of histone modifications. Biochim Biophys Acta. 2006 Dec;1764(12):1932-9;
http://www.ncbi.nlm.nih.gov/pubmed/17015046.
135
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999, Section 6.4.1,
“Acoustic Power Transmission”; http://www.nanomedicine.com/NMI/6.4.1.htm.
 42

The chromallocyte design includes an extensible primary manipulator 4 μm long and 0.55 μm in diameter
called the proboscis that is used to spool up chromatin strands via slow rotation when inserted into the cell
nucleus (image sequence, below; images by E-spaces). After spooling (images A and B), a segmented
funnel assembly is extended around the spooled bolus of DNA, fully enclosing and sequestering the old
genetic material (image C). The new genetic material can then be discharged into the nucleus through the
center of the proboscis by pistoning from internal storage vaults (image D), while the old chromatin that is
sequestered inside the sealed leakproof funnel assembly is forced into the storage vaults as space is vacated
by the new chromatin that is simultaneously being pumped out.

A B

C D

The chromallocyte can employ a mobility system similar to the microbivore grapple system, possibly
including a solvation wave drive 136 to help ensure smooth passage through cell plasma membrane and
nuclear membrane.

From the cryonics perspective, chromallocytes should be regarded as prototype cell repair machines. They
can selectively insert, extract, or replace specific cellular components on a cell-by-cell basis. The devices
could perform this function on any cell or tissue that remains in, or has been rewarmed to, a reliquidified
state.

136
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999, Section 9.4.5.3,
“Solvation Wave Drive”; http://www.nanomedicine.com/NMI/9.4.5.3.htm.
 43

1.2.4 Vasculoid-Class Nanorobots

The vasculoid 137 is a single, complex, multisegmented medical
nanorobotic system capable of duplicating all essential thermal
and biochemical transport functions of the blood, including
circulation of respiratory gases, glucose, hormones, cytokines,
waste products, and cellular components. This nanorobotic
system, a very aggressive and physiologically invasive
macroscale nanomedical device comprised of ~500 trillion stored
or active individual nanorobots, conforms to the shape of existing
blood vessels and serves as a complete replacement for natural
blood. In simplest terms, the vasculoid is a watertight coating of
nanomachinery distributed across the lumenal surface of the
entire human vascular tree (image, right). It uses a ciliary array
to transport important nutrients and biological cells to the tissues,
containerized either in “tankers” (for molecules) or in “boxcars”
(for cells).

The vasculoid appliance is described in greater detail in Section

4.6. It represents a class of medical nanorobotic systems that consist of multiple nanorobot types
performing multiple complex medical tasks, often intended for long-term or permanent residence in the
human body.

1.2.5 Advantages of Medical Nanorobots

Although biotechnology makes possible a greatly increased range and efficacy of treatment options
compared to traditional approaches, with medical nanorobotics the range, efficacy, comfort and speed of
possible medical treatments further expands enormously. Medical nanorobots will be essential whenever
the damage to the human body is extremely subtle, highly selective (e.g., specific organ, tissue, or cell
type), or time-critical (as in head traumas, burns, or fast-spreading diseases), or when the damage is very
massive, overwhelming the body’s natural defenses and repair mechanisms – pathological conditions from
which it is often difficult or impossible to recover at all using current or easily foreseeable biotechnological
techniques.

While it is true that many classes of conventional medical problems may be at least partially resolved using
existing treatment alternatives, 138 it is also true that as the chosen medical technology becomes more
precise, active, and controllable, the range of options broadens and the quality of the options improves.
Thus the question is often not whether medical nanorobots are absolutely required to accomplish a given
medical objective. In some cases, they are not – though of course there are some things that only
biotechnology and nanotechnology can do, and some other things that only nanotechnology can do.
Rather, the important question is which approach offers a superior outcome for a given medical problem,
using any reasonable metric of treatment efficacy. For virtually every class of medical challenge, a mature

137
Freitas RA Jr., Phoenix CJ. Vasculoid: A personal nanomedical appliance to replace human blood. J Evol Technol. 2002
Apr;11:1-139; http://www.jetpress.org/volume11/vasculoid.pdf.
138
e.g., https://en.wikipedia.org/wiki/CRISPR#Applications.
 44

medical nanorobotics technology offers a wider and more effective range of treatment options than any
other solution. In the case of cryostasis revival, it would appear that only medical nanorobots will be
sufficient to meet the challenge (Section 4.17).

A few of the most important advantages of medical nanorobotics over present-day and anticipated future
biotechnology-based medical and surgical approaches include: 139

1. Speed of Treatment. Doctors may be surprised by the incredible quickness of nanorobotic

action when compared to methods relying on self-repair. Mechanical nanorobotic therapeutic systems
should reach their targets up to ~1,000 times faster, all else equal, and treatments which require ~105 sec
(~days) for biological systems to complete may require only ~102 sec (~minutes) using nanorobotic
systems. 140

2. Control of Treatment. Present-day biotechnological entities are not very programmable and
cannot easily be switched on and off conditionally (while following complex multidecision trees) during
task execution. Even assuming that a digital biocomputer 141 could be installed in, for example, a fibroblast,
and that appropriate effector mechanisms could be attached, such a biorobotic system would necessarily
have slower clock cycles, 142 less capacious memory per unit volume, and longer data access times,
implying less diversity of action, poorer control, and less complex executable programs than would be
available in diamondoid nanocomputer-controlled nanorobotic systems. The mechanical or electronic
nanocomputer approach 143 emphasizes precise control of action, 144 including control of physical placement,
timing, strength, structure, and interactions with other (especially biological) entities.

3. Verification of Treatment. Nanorobotic-enabled endoscopic nanosurgery 145 will include

comprehensive sensory feedback enabling full VR telepresence permitting real-time surgery into cellular

139
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999, Section 1.3.3,
“Biotechnology and Molecular Nanotechnology”; http://www.nanomedicine.com/NMI/1.3.3.htm.
140
Freitas RA Jr. Microbivores: Artificial mechanical phagocytes using digest and discharge protocol. J Evol Technol
2005;14:1-52; http://www.jetpress.org/volume14/freitas.html.
141
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999, Section 10.2.3,
“Biocomputers”; http://www.nanomedicine.com/NMI/10.2.3.htm. Guet CC, Elowitz MB, Hsing W. Combinatorial synthesis
of genetic networks. Science. 2002 May 24;296(5572):1466-70;
http://science.sciencemag.org/content/sci/296/5572/1466.full.pdf. Yokobayashi Y, Weiss R, Arnold FH. Directed evolution of
a genetic circuit. Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16587-91;
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC139187/. Basu S, Mehreja R, Thiberge S, Chen MT, Weiss R. Spatiotemporal
control of gene expression with pulse-generating networks. Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6355-60;
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC404049/. Basu S, Gerchman Y, Collins CH, Arnold FH, Weiss R. A synthetic
multicellular system for programmed pattern formation. Nature. 2005 Apr 28;434(7037):1130-4;
http://macpost.caltech.edu/groups/fha/publications/Basu_Nature2005.pdf.
142
Basu S, Mehreja R, Thiberge S, Chen MT, Weiss R. Spatiotemporal control of gene expression with pulse-generating
networks. Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6355-60; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC404049/.
143
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999, Section 10.2,
“Nanocomputers”; http://www.nanomedicine.com/NMI/10.2.htm.
144
Freitas RA Jr. Computational tasks in medical nanorobotics. In: Eshaghian-Wilner MM (ed) Bio-inspired and Nano-scale
Integrated Computing. Wiley, New York, 2009; http://www.nanomedicine.com/Papers/NanorobotControl2009.pdf.
145
Freitas RA Jr. “Chapter 23. Comprehensive Nanorobotic Control of Human Morbidity and Aging,” in Gregory M. Fahy,
Michael D. West, L. Stephen Coles, and Steven B. Harris, eds, The Future of Aging: Pathways to Human Life Extension,
Springer, New York, 2010, Section 6.3.5.3; http://www.nanomedicine.com/Papers/Aging.pdf.
 45

and subcellular tissue volumes. Using a variety of communication modalities, 146 nanorobots will be able to
report back to the attending physician, with digital precision and ~MHz bandwidth, 147 a summary of
diagnostically- or therapeutically-relevant data describing exactly what was found prior to treatment, what
was done during treatment, and what problems were encountered after treatment, in every cell or tissue that
was visited and treated by the nanorobot. A comparable biological-based approach relying primarily upon
chemical messaging must necessarily be slow with only limited signaling capacity and bandwidth.

4. Minimal Side Effects. Almost all drugs have significant side effects, such as conventional
cancer chemotherapy which typically causes hair loss and vomiting, although computer-designed drugs can
have higher specificity and fewer side effects than earlier drugs. Carefully tailored cancer vaccines under
development starting in the late 1990s were expected unavoidably to affect some healthy cells. Even well-
targeted drugs are distributed to unintended tissues and organs in low concentrations, 148 although some
bacteria can target a few organs fairly reliably without being able to distinguish individual cells. By
contrast, mechanical nanorobots may be targeted with virtually 100% accuracy to specific organs, tissues,
or even individual cellular addresses within the human body. 149 Such nanorobots should have few if any
side effects, and will remain safe even in large dosages because their actions can be digitally self-regulated
using rigorous control protocols 150 that affirmatively prohibit device activation unless all necessary
preconditions have been met and remain continuously satisfied. Almost three decades ago, Fahy 151
observed that these possibilities could transform “drugs” into “programmable machines with a range of
sensory, decision-making, and effector capabilities [that] might avoid side effects and allergic
reactions...attaining almost complete specificity of action....Designed smart pharmaceuticals might activate
themselves only when, where, and if needed.” Additionally, nanorobots may be programmed to harmlessly
remove themselves from the site of action, or conveniently excrete themselves from the body, after a
treatment is completed. By contrast, spent biorobotic elements containing ingested foreign materials may
have more limited post-treatment mobility, thus lingering at the worksite causing inflammation when
naturally degraded in situ or removed. (It might be possible to design artificial eukaryotic biorobots having
an apoptotic pathway 152 that could be activated to permit clean and natural self-destruction, but any
indigestible foreign material that had been endocytosed by the biorobot could still cause inflammation in
surrounding tissues when released).

5. Faster and More Precise Diagnosis. The analytic function of medical diagnosis requires
rapid communication between the injected devices and the attending physician. If limited to chemical

146
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999, Chapter 7,
“Communication”; http://www.nanomedicine.com/NMI/7.1.htm.
147
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999, Section 7.3,
“Communication Networks”; http://www.nanomedicine.com/NMI/7.3.htm.
148
Davis S. Chapter 16. Biomedical applications of particle engineering. In: Coombs RRH, Robinson DW (eds)
Nanotechnology in Medicine and the Biosciences. Gordon & Breach Publishers, Netherlands, 1996, pp. 243-262.
149
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999, Chapter 8,
“Navigation”; http://www.nanomedicine.com/NMI/8.1.htm. Freitas RA Jr. Pharmacytes: an ideal vehicle for targeted drug
delivery. J Nanosci Nanotechnol 2006 Sep-Oct;6(9-10):2769-2775; http://www.nanomedicine.com/Papers/JNNPharm06.pdf.
150
Freitas RA Jr. Computational tasks in medical nanorobotics. In: Eshaghian-Wilner MM (ed) Bio-inspired and Nano-scale
Integrated Computing. Wiley, New York, 2009; http://www.nanomedicine.com/Papers/NanorobotControl2009.pdf.
151
Fahy GM. Molecular nanotechnology and its possible pharmaceutical implications. In: Bezold C, Halperin JA, Eng JL
(eds) 2020 Visions: Health Care Information Standards and Technologies. U.S. Pharmacopeial Convention Inc., Rockville
MD, 1993, pp. 152-159.
152
Freitas RA Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX, 1999, Section 10.4.1.1,
“Apoptosis”; http://www.nanomedicine.com/NMI/10.4.1.1.htm.
Another random document with
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ease and slight alteration it was possible for the two geared engines
supplied to the Great Western Railway by the Haigh Foundry to have been
altered to ordinary direct action engines.
Large wheels were also to be used for the tender, the axles passing
through the water-tank, so that the centre of gravity was lowered.
James Pearson, the locomotive superintendent of the Bristol and Exeter
Railway, obtained a patent on October 7th, 1847, for a double locomotive.
Fairlie’s “Little Wonder” narrow-gauge engines were probably suggested by
Pearson’s design of 1847; whilst the latter’s famous broad-gauge double-
bogie tanks were decidedly evolved from his earlier form of locomotive.
The boiler was to have the fire-box in the centre, the latter being divided
into two parts, connected below the furnace doors; the driving axle was
across this central foot-plate, to allow of very large wheels and a low centre
of gravity. Each boiler (there being practically two, one each side of the
central double fire-box) was carried on a four-wheel bogie, so that the
locomotive was carried on ten wheels, as in the later design. The bogie
frames were connected by tension-rods, passing outside the fire-box. India-
rubber springs were employed, their use being to allow each bogie to adjust
itself to any inequality of the road, and to bring the bogies back to the
straight position on an even road. The coke was to be stowed in bunkers
over the boilers, and the water could be either in tanks between the tops of
the boilers and the coke bunkers, or a separate tender could be provided.
The steam domes were on the fire-box, and were to be of abnormal height,
and connected over the head of the foot-plate, thus forming the roof of the
cab. An exhaust fan was fixed in the smoke-box to draw the heated air
through the tubes and discharge it up the chimney, or it could be used again
as a hot blast for the furnace, and a chimney and a smoke-box were
provided for each boiler. The fans were to be driven by pulleys off one of the
axles, and it was claimed that, as the exhaust steam was not required for
the purpose of creating a blast, extra large exhaust pipes could be used,
and the cylinders thereby relieved of “back pressure.” The cylinders were
outside, and the valves were beyond the cylinders. These were fixed
between the wheels of one of the bogies. The general design of this engine,
as shown in the drawings, was very ingenious, and is certainly the most
symmetrical “double-ended” type of engine we have seen illustrated.
Pearson for some reason did not construct an engine after this style, but
produced the well-known 9ft. “single” (double-bogie) tanks instead.
The third patent now to be described had also for its leading feature
extra large driving wheels. The specification is that of Charles Ritchie, of
Aberdeen, the patent being granted to him on March 2nd, 1848. The
principal feature was the providing of two piston-rods to each piston, one on
each side. Four driving wheels were proposed, one pair placed in front of
the smoke-box and one pair behind the fire-box. The cylinders were outside,
and were, of course, fixed at an equal distance between the two pairs of
driving wheels. One pair of carrying wheels was to be used, placed below
the cylinders. It was claimed that this arrangement of pistons and
connecting-rods exactly balanced the reciprocating parts of the machinery,
and therefore abolished oscillation. Another improvement related to the
slide-valves, the starting, stopping, and reversing of the engine, together
with the expansive working of the steam, the whole to be controlled by a
wheel on the foot-plate, connected by cogs with the link of the valve gear.
Other improvements were compensating safety valves, an “anti-primer,”
and an improved feed-water apparatus. The last is described as follows:
—“Upon steam being admitted from the boiler into the cylinder, through the
steam-port, the piston will be acted upon, and the ram be withdrawn; the
water will then raise the valve and enter the barrel, to occupy the space
previously occupied by the ram. By this time the piston will have acted upon
a lever, so as to cause the slide-valve to uncover one port and cover the
other, thereby allowing the steam on the other side of the piston to escape
through the exhaust pipe.
“The piston will now be impelled in a contrary direction, and the ram
entering the barrel will cause the one valve to be closed and the other to be
opened by pressure of the water therein, which, as the ram advances, will
be forced into the boiler.”
Another part of the specification related to an “anti-fluctuator.” A partition-
plate was to be fixed between the tube-plate and the fire-box, and the water
was to be let into the boiler at the fire-box end, and would only reach that
portion of the boiler beyond the fire-box by flowing over the top of the
partition-plate. By this means the fire-box would always be covered with
water. It will be seen that the specification contained several useful
propositions, which, however, do not appear to have been put into practice.
 Fig. 56.—TIMOTHY HACKWORTH’S “SANSPAREIL NO. 2”

We have previously, upon more occasions than one, shown the

important position occupied in the evolution of the steam locomotive by the
engines built or designed by Timothy Hackworth. We now have to give an
account of his last locomotive, the “Sanspareil No. 2.”
A comparison of the drawings of this engine (copies of which are in our
possession) with Hackworth’s earlier efforts of 20 years before, clearly
discloses the remarkable strides made in the improvement of the locomotive
during that period, and also most clearly shows that in 1849 Hackworth was
still in the very van of locomotive construction, even as he had been in the
days of his “Royal George.”
The “Sanspareil No. 2” (Fig. 56) was constructed by Timothy Hackworth
at his Soho Engine Works at Shildon. The patent was obtained in the name
of his son, the late John Wesley Hackworth. We are indebted to the executor
of the will of Timothy Hackworth for many of the following details concerning
the engine now under review.
The locomotive was of the six-wheel “single” type, with outside bearings
to the L. and T. wheels, and inside bearings of the driving wheels. The
cylinders were inside. A cylindrical steam dome was placed on the boiler
barrel close to the smoke-box. The fire-box was of the raised pattern, and on
it was an encased Salter safety valve. Cylindrical sand-boxes were fixed on
the frame-plates in front of the driving wheels. The principal dimensions of
the engine were:—Driving wheels, 6ft. 6in. diameter; leading and trailing, 4ft.
diameter; cylinders, 15in. diameter, 22in. stroke. Weight in working order:—
L., 8 tons 6 cwt.; D., 11 tons 4 cwt.; T., 4 tons 5 cwt. Total, 23 tons 15 cwt.
It would be well if we mentioned the principal novelties in construction—
viz.: Welded longitudinal seams in boiler barrel; the boiler was connected to
the smoke-box and fire-box by means of welded angle-irons, instead of the
usual riveted angle-irons; the lagging of the boiler was also covered with
sheet-iron, as is now general, instead of the wood being left to view, as was
at that time the usual practice.
A baffle-plate was fitted at the smoke-box end of tubes, as well as at the
fire-box end.
The pistons and rods were made of wrought-iron in one forging.
The valves were constructed under Hackworth’s patent, and were
designed to allow a portion of the steam required to perform the return
stroke to be in the cylinder before the forward stroke was completed, and
thus to form a steam cushion between the piston and cylinder covers. Such
working was said to economise 25 to 30 per cent. of fuel.
The engine conveyed 200 tons 45 miles in 95 minutes, consuming 21
cwt. of coke, and evaporating 1,806 gallons of water. She also drew a train
of six carriages over the same distance without a stop, in 63 minutes, with
an expenditure of 13 cwt. of coke and 1,155 gallons of water.
Upon the completion of this engine, J. W. Hackworth sent the following
challenge to Robert Stephenson:—
“Sir,—It is now about 20 years since the competition for the premium of
locomotive superiority was played off at Rainhill, on the Liverpool and
Manchester Railway. Your father and mine were the principal competitors.
Since that period you have generally been looked to by the public as
standing first in the construction of locomotive engines. Understanding that
you are now running on the York, Newcastle and Berwick Railway a
locomotive engine which is said to be the best production that ever issued
from Forth Street Works, I come forward to tell you publicly that I am
prepared to contest with you, and prove to whom the superiority in the
construction of locomotive engines now belongs.
“At the present crisis, when any reduction in the expense of working the
locomotive engine would justly be hailed as a boon to railway companies,
this experiment will no doubt be regarded with deep interest as tending to
their mutual advantage. I fully believe that the York, Newcastle and Berwick
Railway Company will willingly afford every facility towards the carrying out
of this experiment.
 “Relying upon your honour as a gentleman, I hold this open for a
fortnight after the date of publication.

“I am, Sir, yours, etc., John W. Hackworth.”

We do not think Robert Stephenson accepted the challenge; at all

events, no records of such a competition have ever been made public, and
had it taken place the victor would have doubtless well published the result.
The “Sanspareil” frequently attained a speed of 75 miles an hour on
favourable portions of the line. She was sold to the North Eastern Railway
by the executors shortly after the death of Timothy Hackworth, something
like £3,000 being obtained for the engine, which continued to work upon the
North Eastern Railway until recent years, having, of course, been rebuilt
during the long time it was in active service.
We have now to describe another specimen of the locomotives
constructed by the celebrated firm of Bury, Curtis and Kennedy. This
locomotive was one of the last engines built by the firm before its final
dissolution. The “Wrekin” was a six-wheel engine with inside bar frames and
inside cylinders, and was constructed for the Birmingham and Shrewsbury
Railway in 1849.
The special points noticeable in the construction of the engine in
question are the width of the framing, which was arranged horizontally
instead of vertically, and only two bearings to each axle. The axle-boxes of
the leading wheels were bolted to the frames, those of the other wheels
being welded to the frames, and the cylinders were also directly affixed to
the framing. An advantage claimed by the builders, as resulting from the
method of construction employed, was that the weight being placed entirely
within the wheels, such weight had a tendency to press down the axle
between the bearings, and so counteract the constant tendency arising from
the flanges of the wheels, when pressing against the edge of the rails,
especially in passing round curves.
The cylinders were 15in. diameter, the stroke being 20in. The driving
wheels were 5ft. 7in. diameter, the leading 4ft. 1in. and the trailing 3ft. 7in.
The boiler contained 172 brass tubes, 11ft. 6in. long and 2⅛in. external
diameter. The heating surface was: Tubes, 1,059 sq. ft.; fire-box, 80 sq. ft.;
total, 1,139 sq. ft. Grate area, 15 sq. ft.
 No steam dome was provided, the main steam-pipe being of iron, with a
longitudinal opening ³/₁₆th inches wide along the top; this pipe extended to
the smoke-box, at which end of it the regulator valve was placed; the
actuating-rod passing through the main steam-pipe from end to end. Two
encased Salter safety valves were fixed on the fire-box. The wheel base of
the “Wrekin” was: leading to driving, 8ft. 1in.; driving to trailing, 6ft. 11in.
In 1849 the Vulcan Foundry Company supplied the Caledonian Railway
with an engine known as “No. 15.” In general appearance the locomotive
was very similar to Allan’s “Velocipede” engine on the London and North
Western Railway.
“No. 15” (Fig. 57) was a six-wheel engine, with inclined outside cylinders,
15in. diameter and 20in. stroke. The driving wheels were 6ft. diameter,
leading and trailing wheels 3ft. 6in. diameter. The boiler barrel was 9ft. 9in.
long and 3ft. 6¾4in. diameter, containing 158 brass tubes of 1¾in. external
diameter. Wheel base, L. to D., 6ft.; D. to T., 6ft. 6½in. The chimney was 6ft.
6in. high; on the centre of the boiler was a man-hole, surmounted by a
column safety valve of Salter’s pattern, the blowing-off steam pressure being
90lb. The steam dome was of brass, placed on the raised fire-box, and
surmounted with a second Salter’s safety valve. The driving and leading
wheels were provided with underhung springs, but the trailing wheels had
the springs over the axle-boxes. These latter springs were of elliptic shape,
and were provided with a screw device fixed on the foot-plate, by means of
which the weight was taken off the trailing wheels and thrown upon the
driving wheels.
In addition to the semi-circular brass name-plates (i.e., Caledonian
Railway) affixed to the splashers of the driving wheels, brass number-plates
of diamond shape (12in. long by 6in. diameter) were fixed on the buffer
beams of “No. 15.” The tender was supported on four wheels, 3ft. 6in.
diameter, and held 800 gallons of water.
 Fig. 57.—CALEDONIAN RAILWAY ENGINE, “No. 15”

During June, 1849, “No. 15” made a number of trial trips between
Glasgow and Carlisle, with seven, eight, and nine coaches of an average
weight of five tons each, the weight of the engine and tender being 28 tons.
On the trips to Glasgow the Beattock Summit had, of course to be climbed.
This consists of 10 miles of stiff gradients, varying between 1 in 75, 80, and
88. The run of 13½ miles from Beattock to Elvanfoot, consisting of the 10
miles just described and of 3½ down at 1 in 100, was negotiated by “No. 15”
in 33 minutes, with a train of six coaches; with seven coaches the time was
41 minutes, and with a pilot and eleven coaches, 30 minutes, or at the rate
of 27 miles an hour. These were considered exceptionally good specimens
of hill-climbing performances 48 years back, but are, of course, entirely out
of comparison with modern Caledonian records over the same line with
much heavier trains.
 Fig. 58.—“MAC’S MANGLE,” No. 227, L. & N.W.R.

McConnell, the locomotive superintendent of Wolverton, turned out

several remarkable locomotives for the London and North Western Railway,
and No. 227, or, as she was generally called, “Mac’s Mangle,” (Fig. 58), was
one of these peculiar specimens of McConnell’s design. The cylinders were
of large size, being 18in. diameter, with a 24in. stroke; they were outside, as
were also the axle bearings—a very uncommon combination. No. 227 was a
six-wheel “single” engine, the driving wheels being 6ft. 6in. diameter, and the
leading and trailing wheels 4ft. diameter. The fire-box was of the raised
pattern, and a Salter safety valve (encased) was fixed on it. A huge steam
dome was provided, located, originally, close to the smoke-box end of the
boiler barrel, but afterwards (in 1850) placed near the fire-box end, over the
driving wheels. The boiler-heating surface of “Mac’s Mangle” was 1,383 sq.
ft. No. 227 enjoyed but a short locomotive career, being built in April, 1849,
and “scrapped” in May, 1863. It is stated that in consequence of the extreme
width of this engine, caused by outside cylinders being employed in
conjunction with outside axle-boxes, it became necessary to set back the
platforms at some of the stations, so that the engine could clear these
erections without coming to grief.
 Fig. 59.—“PRESIDENT,” ONE OF McCONNELL’S
“BLOOMERS,” L. & N.W.R AS ORIGINALLY
BUILT
In 1850 McConnell designed a very powerful class of passenger engines
for the L. and N. W. R. These are generally called the “Bloomers.”
“President” (Fig. 59) illustrates this favourite class of L. and N. W. R.
locomotive, when built. The cylinders were inside, 16in. diameter, with a
stroke of 22in. The driving wheels were 7ft. in diameter. The heating surface
was 1,152 sq. ft. These engines weighed 28¾ tons. (Fig. 60) is from a photo
of a “Bloomer” as rebuilt by Ramsbottom.

Fig. 60.—ONE OF McCONNELL’S “BLOOMERS” AS

REBUILT BY RAMSBOTTOM
 CHAPTER X.
The locomotive exhibits of 1851—The “Hawthorn”—Wilson’s two-boiler engine, the
“Duplex”—Fairbairn’s tank engine—The S.E.R. “Folkestone” on Crampton’s system—
Sharp’s “single” engines for the S.E.R.—J. V. Gooch’s designs for the Eastern Counties
Railway—The “Ely,” Taff Vale Railway—Beattie’s “Hercules”—A much-vaunted
locomotive, McConnell’s “300” L. & N.W.R—London and Birmingham in two hours—The
chief features of “300”—Competitive trials with other engines—Coal v. coke—An earlier
“recessed” boiler—Dodd’s “Ysabel”—The first compound locomotive—Another Beattie
design—Pasey’s compressed air railway engine—Its trial trips on the Eastern Counties
Railway—The original (Great Northern engines Sturrock’s masterpiece, “No. 215,”
G.N.R.)—Pearson’s famous 9ft. “single” double-bogies, Bristol and Exeter Railway—
Rebuilt with 8ft. drivers, and a tender added by the G.W.R.—More old Furness Railway
engines—Neilson’s outside cylinder locomotives—A powerful goods engine on the
Maryport and Carlisle Railway—Gooch’s 7ft. coupled broad-gauge locomotives—His first
narrow-gauge engines.
The premier International Exhibition, which, as all the world well knows, was held
in Hyde Park, London, 1851, brought together quite a respectable collection of railway
appliances. The British exhibitors showed the following locomotives:—
London and North Western Railway’s “Cornwall” and “Liverpool.”
Great Western Railway’s “Lord of the Isles.”
Hawthorne’s express, “Hawthorn.”
Adams’ combined engine and carriage, “Ariel’s Girdle,”
built by Wilson and Co., Leeds.
England’s light locomotive, built by Fairbairn.
Fairbairn’s tank engine.
South Eastern Railway’s “Folkestone.”
E. B. Wilson and Co.’s double boiler tank engine.

Several of these have been described in an earlier chapter, whilst details of other
types (such as the “Lord of the Isles” type) have also been given, so that it is not
necessary to describe such designs again. We have, however, to give particulars of
Hawthorne’s express, Fairbairn’s tank, the “Folkestone,” and Wilson’s “double boiler”
tank engine. The dimensions of the first are: cylinders, 16in. diameter, 22in. stroke;
driving wheels, 6ft. 6in.; leading and trailing wheels, 3ft. 9in. diameter; heating surface
of fire-box, including water bridge, 110 sq. ft.; tubes, 865.4 sq. ft. The tubes were of
brass, of 2in. external diameter, and 158 in number.
The “Hawthorn” had inside cylinders and double sandwich frames, a raised fire-
box, with an enclosed safety valve, no dome, but a perforated steam-pipe for the
collection of the steam was provided. The engine was designed for running at 80 miles
an hour; the special features of the engine being double-compensating beams for
distributing the weight uniformly on all the wheels, equilibrium slide-valves, and an
improved expansion link suspended from the slide-valve rods. Instead of fitting a
spring to each wheel, two only were placed on each side of the engine between the
wheels. These springs were inverted, and sustained by central straps attached to the
framing. Their ends were connected by short links to the wrought-iron double-
compensating beams placed longitudinally on each side of the engine, inside and
beneath the framing.
The two inner contiguous ends of these beams were linked by a transverse pin to
an eye at the bottom of the axle-box of the driving axle, whilst the opposite ends of the
beams were respectively linked in a similar manner to eyes on the top of the leading
and trailing axle-boxes. The action of these beams was obvious. By them a direct and
simultaneous connection was given to all the axle bearings, and consequently a
uniform pressure was always maintained on all the wheels, irrespective of
irregularities on the permanent-way. The slide valves were placed on vertical faces in
a single steam chest, located between the two cylinders. One slide-valve had a plate
cast on its back, and the other had an open box cast on its back to receive a piston,
which had its upper end parallel with the valve face. This piston was fitted steam-tight
in the box, and its planed top bore against the face of the plate in working. By this
arrangement the slides were relieved from half of the steam pressure; and to assist a
free exhaust, a port was made in the back plate of one of the slides, so providing an
additional exit for the spent steam by means of the piston and the exhaust ports of the
opposite valve.
The expansion link was placed in such a position as to allow the bottom of the
boiler to be quite near the axle. The link, instead of being fixed to the ends of the
eccentric-rods, so as to rise and fall with them when the reversing lever was moved,
was suspended from its centre, by an eye, from the end of the slide-valve spindle.
This removed the weight of the link, etc., from off the reversing gear. The eccentric-
rods were jointed to the opposite ends of the link slide-block, to secure steadiness and
durability of the parts. It was claimed that this method of a fixed link-centre as fitted to
the “Hawthorn” ensured a more correct action of the valves.
Wilson and Co., of the Railway Foundry, Leeds, exhibited a curious tank engine at
the Exhibition of 1851, called the “Duplex,” in consequence of it being provided with
two boilers. The idea of the designer was to obtain sufficient steam from an engine of
light weight to haul a heavy train. The original drawings of this engine are still in the
possession of Mr. David Joy, who designed it; and at first it was proposed to build the
“Duplex” with three cylinders and six-coupled wheels, but afterwards fresh drawings
were prepared, and it was from these latter ones that the engine was built. The two
boilers were placed side by side, and these each measured 10ft. 6in. long by 1ft. 9in.
diameter, and together contained 136 tubes of 1¾in. diameter, the heating surface of
which was 694 sq. ft., that of the fire-box being 61 sq. ft., making a total of 755 sq. ft.
The cylinders were outside, their diameter being 12½in., and the stroke 18in. The
leading wheels were 3ft. 6in. diameter; the driving and trailing (coupled) 5ft. diameter.
Some other dimensions were:—Total length, 24ft. 3in.; breadth, 5ft. 3in.; height from
rail to top of chimney, 13ft. 6in.; weight, empty, only 16 tons, with fuel and water 19
tons 17 cwt. The capacity of tank was 520 gallons, sufficient for a journey of 25 miles;
coke bunker, 42 cubic feet, equal to 26 bushels, or 15 cwt. The “Duplex” was sold to a
Dutch railway after the Exhibition, and its further career is, therefore, unknown to
those interested in it.
 Fairbairn’s tank locomotive was of the “well” type, supported on six wheels, the
driving pair being 5ft. diameter, and the L. and T. each 3ft. 6in. diameter. The cylinders
were inside, measuring 10in. by 15in. stroke. The boiler was 8ft. long by 3ft. diameter,
and contained 88 brass tubes of 2in. diameter. The heating surface amounted to 480
sq. ft. The internal fire-box was of copper, and measured 2ft. 5in. long, 3ft. wide, and
3ft. 5in. deep. The tank behind and under the foot-plate held 400 gallons of water. The
coke consumption of this little engine was only 10lb. per mile with trains of six
carriages, the weight in working order only 13 tons; and it may interest our readers to
know that this diminutive locomotive was described as “a fair specimen of the heavier
class of tank engine.

Fig. 61.-THE “FOLKESTONE,” A LOCOMOTIVE ON CRAMPTON’S

SYSTEM. BUILT FOR THE S.E.R., 1851
The engine calling for the greatest attention at the Exhibition of 1851 was the
“Folkestone” (Fig. 61), exhibited by the South Eastern Railway. This was an engine
built by R. Stephenson and Co., under one of Crampton’s patents, but the principal
feature in its design was an intermediate driving axle, connected by means of outside
cranks, and coupling-rods to the driving wheels, which were (under Crampton’s
patent) behind the fire-box, the axle extending across the foot-plate. It will be well,
perhaps, if we at this point reiterate the fact that the method of working locomotives by
means of an intermediate crank-shaft was not introduced by Crampton, it having been
used some years previously by W. B. Adams, not to mention some of the early
Stockton and Darlington Railway engines, where the same arrangement was
employed, but with vertical cylinders. Readers will, therefore, see it is incorrect to
describe locomotives with this system of machinery as “Crampton’s patent,” although it
is quite possible for a “Crampton patent” locomotive to be provided with an
intermediate driving shaft, as was the case with the “Folkestone.”
Eight engines of this type were built by Stephenson and Co. for the South Eastern
Railway, and were numbered 136 to 143, the first of which was named “Folkestone.”
These engines were supported by six wheels, a group of four being arranged close
together at the smoke-box end. Their diameter was 3ft. 6in. The driving wheels were
6ft. in diameter, the wheel base 16ft. These engines weighed 26¼ tons each, of which
only 10 tons were on the driving wheels, the remainder of the weight being supported
by the four leading wheels. The cylinders were inside, 15in. diameter, and the stroke
22in. The fire-box top was flush with the boiler barrel, the straight lines of which were
unrelieved by a dome, but an encased safety valve was fixed near the back of the fire-
box top. The boiler contained 184 tubes, of 2in. diameter and 11ft. in length.
The “Folkestone” ran its trial trip on Monday, March 31st, 1851, when Mr.
McGregor, the chairman of the South Eastern Railway, Mr. R. Stephenson, the builder
of the engine, Mr. Barlow, the South Eastern engineer, and Mr. Cudworth, the South
Eastern locomotive superintendent, were present. From London Bridge to Redhill no
great speed could be attained, as a Brighton train was in front; but beyond the latter
station, and with a train of nine carriages, the 19½ miles to Tonbridge were covered in
19½ minutes, a maximum speed of 75 miles an hour being attained. After a short stop,
the journey to Ashford was resumed, and that town was reached in 20½ minutes after
leaving Tonbridge. The times and distances were as follow:—Redhill to Tonbridge, 19
miles 47 chains, start to stop in 19½ minutes; Tonbridge to Ashford, 26 miles 45
chains, start to stop in 20½ minutes, or at the rate of 78 miles an hour; the whole 46
miles 12 chains being covered in 40 minutes, running time, or, including the stop at
Tonbridge, in 43 minutes. It must be remembered that the line between Redhill and
Ashford is, perhaps, the most level and straight in England for so long a distance.
These eight engines did not prove very successful in general working, and they
were afterwards rebuilt as four-coupled engines, an ordinary cranked axle with wheels
being provided in place of the intermediate driving shaft.
It will not be out of place if we here mention eight “single” engines built by Sharp
Bros. in 1851 for the South Eastern Railway, and numbered 144 to 151. The general
dimensions were similar to the Cramptons, except that the wheel base was only 15ft.,
and that the heating surface was 1,150 sq. ft. The admission of the steam to the
cylinders was controlled by a hand lever, with catch and notches, similar to and placed
by the side of the ordinary reversing lever. Six eccentrics were on the driving axle, two
of them working the pumps. The framing and springs of these engines were
afterwards perpetuated by Cudworth in his later and better known types of South
Eastern locomotives.
 Fig. 62.—ONE OF J. V. GOOCH’S “SINGLE” TANK ENGINES,
EASTERN COUNTIES RAILWAY
The locomotives of the despised “Eastern Counties,” that were designed about
1850 by Mr. J. V. Gooch, will now be concisely described. They were of three kinds—
viz., “single” tanks, “single” express, and four-wheels-coupled tender engines. Of the
tanks, three sizes were constructed, chiefly at the “Hudson Town” (or Stratford Works).
The largest of these were provided with outside cylinders, 14in. diameter and 22in.
stroke, the boiler being 10ft. 6in. long, and containing 164 tubes of 1³/₁₆th in. diameter.
The leading and trailing wheels had outside bearings, the driving wheels being
provided with inside bearings only. A steam dome was placed over the raised fire-box,
and a screw-lever safety valve on the boiler barrel. The water was stored in two tanks,
fixed between the frames, one below the boiler and the other beneath the foot-plate.
These tank engines were known as the “250” class, and some of our readers may
recollect that when Peto, Brassey and Betts leased the London, Tilbury and Southend
Railway, engines of this design were used to work the traffic on that railway. We
understand it is now 20 years since the last of them (No. 08) reached the final bourne
of worn-out locomotives—the “scrap heap.”
The dimensions of the smallest class of these tanks (Fig. 62) were: Cylinders, 12in.
diameter, 22in. stroke; boiler, 10ft. long and 3ft. 2in. diameter, 127 tubes of 1⅞th in.
diameter; the total heating surface was 709 sq. ft.; grate area, 9.7 sq. ft. The driving
wheels were 6ft. 6in. diameter, and the L. and T. 3ft. 8in. The total weight of these
engines was 23 tons 19 cwt., of which 9 tons 14 cwt. was on the driving axle. The
wheel base was: L. to D., 6ft. 3in.; D. to T., 5ft. 9in.
J. V. Gooch’s four-coupled, or “Butterflies,” had leading wheels 3ft. 8in. diameter,
and driving and trailing (coupled) 5ft. 6in. Wheel base, L. to D., 6ft. 3in.; D. to T., 7ft.
9in. The cylinders were 15in. diameter, the stroke being 24in. The boilers of this class,
and also of the singles, next to be described, were of the same dimensions as those of
the “250” class of tanks.
 The “single” expresses were provided with 6ft. 6in. driving wheels, and cylinders
15in. diameter and a 22in. stroke; in this class also the leading and trailing wheels
were 3ft. 8in. diameter. The wheel base was 14ft., the driving wheels being 6ft. 9in.
from the leading and 7ft. 3in. from the trailing wheels. Ten engines of this design were
constructed, some at Stratford, and others at the then recently opened Canada Works
of Brassey and Co. at Birkenhead. Their official numbers were from 274 to 283.
The “Ely” (Fig. 63) represents the type of 6-wheel passenger engine in use on the
Taff Vale Railway at this period. She was built in 1851 by Messrs. Kitson and
Company, from Taff Vale designs. She had 13in. cylinders, with 20in. stroke, and four-
wheels-coupled, of 5ft. 3in. diameter. She carried a pressure of 100lbs., she had a
four-wheel tender, carrying 900 gallons of water, and as the gross weight of the tender
was about 11 tons in working order, the gross weight of the engine and tender would
be 33 tons. The “Ely” could not take a train of three carriages, weighing only 21 tons,
up the Abercynon bank of 1 in 40 without the assistance of a “bank” engine.
In 1851 Mr. Beattie, the locomotive superintendent at Nine Elms, built for the
London and South Western Railway the four-wheels-coupled engine, “Hercules,” No.
48. The frames of this engine were of the “lattice” type, examples of which can be still
seen on some of the older Great Northern Railway tanks.
The diameter of wheels was: L., 3ft. 6in.; D. and T., 5ft. 6in.; tender, 3ft. 6in.; wheel
base, L. to D., 7ft. 1in.; D. to T., 6ft. 6in.; T. to leading tender, 7ft. 3½in.; the tender
wheel base being 10ft. 3in. equally divided.

Fig. 63.—“ELY,” A TAFF VALE RAILWAY ENGINE, BUILT IN 1851

The weight was distributed as follows:—Engine, L. axle, 8 tons 17 cwt.; D., 9 tons
17 cwt.; T., 9 tons 16 cwt.; tender, L., 4 tons 19 cwt.; M., 6 tons 19 cwt.; T., 7 tons 10
cwt. The cylinders were 15in. by 22in.; tractive force on rail, 7,500lb.; 1,800 gallons of
water could be carried in the tender tank. The “Hercules” had a flush top boiler, and a
raised fire-box surmounted by a large inverted, urn-shaped dome. This design of
locomotive was a favourite one on the London and South Western Railway for many
years, but the last engine of the kind has now been scrapped.
Having favoured the London and South Western Railway, to equalise matters, we
cannot do better than give a description of a locomotive belonging to its cousin-
german, the London and North Western Railway. The latter was indeed the more
famous, being no other than McConnell’s notorious “No. 300,” (Fig. 64) which, being
introduced with a vast amount of publicity, became a nine days’ wonder, then sank into
quiescent mediocrity, and after a brief locomotive career, was seen no more—a rather
different fate, be it observed, to that of the London and South Western Railway’s
“Hercules.”
It has been stated that only one drawing of this engine exists. This is incorrect; the
writer possesses a complete set of drawings relating to “No. 300,” together with the
whole of the specifications from which the engine was constructed. To reproduce this
specification in detail would give too technical a character to this narrative, and would
try the patience of even the most ardent locomotive enthusiast.
The directors of the London and North Western Railway in 1851 expressed their
determination to run their express trains from London to Birmingham in two hours, and
gave instructions to McConnell, the locomotive superintendent at Wolverton, to design
the necessary locomotives. The salient features of the design were: Inside cylinders,
18in. by 14in.; six wheels, with inside and outside frames; driving wheels, 7ft. 6in.
diameter; leading, 4ft. 6in.; and trailing, 4ft. diameter.
The boiler was 11ft. 9in. long and 4ft. 3¼in. external diameter. The tubes were of
brass, 303 in number, only 7ft. in length, and 1¾in. outside diameter. The crank axle
bearings were—outside, 7in. deep and 10in. in length, the inside ones being 7in. and
4¼in. respectively. The leading and training axles were hollow, the metal being 1½in.
thick, and the hollow centre 4½in. diameter, thus making the total diameter of the
straight axles 7½in. The slide-valves had an outside lap of 1¼in. The principal
innovations were: Coleman’s patent india-rubber springs, fitted below the driving axle
and above the leading and trailing axles, and also to the buffers. McDonnell’s patent
dished wrought-iron pistons, forged in one piece with the piston-rod, and encased with
continuous undulating flat metal packing. The steam-pipe was of flat section, and
passed through a superheating chest in the smoke-box; the steam was thus dried
during its journey from the dome to the cylinders. The great feature of the design was
the arrangement of the fire-box, with a mid-feather, a combustion chamber, hollow
stays for a free supply of air to the fire-box, and the cutting away of the bottom of the
fire-box to obtain clearance for the cranks and yet retain a low centre of gravity with
large driving wheels. Assertion to the contrary notwithstanding, it should be observed
that so much did McConnell insist upon a low centre of gravity that he specially
mentioned it in his patent specification of February 28th, 1852.
A more particular description of the fire-box, etc., is requisite. It extended into the
cylindrical portion of the boiler a distance of 4ft. 9in., so that the boiler tubes were only
7ft. long. The whole length of the fire-box was 10ft. 6in.; depth at front-plate 6ft. 5in., at
door-plate 6ft. 10in.; length on fire-bars 5ft. 10¼in., thus leaving 4ft. 7¾in. for the
portion over the axle and the combustion chamber. At its narrow part (directly at the
top of the recess above the driving axle) the fire-box was only 2ft. 3in. in height; height
at tube-plate 3ft. (beyond the cut away portion); width at tube-plate 3ft. 9in. It will be
noticed that Webb’s “Greater Britain” class of locomotives is designed with the long
fire-box and combustion chamber; but as Mr. Webb, unlike McConnell, does not object
to the high pitched boiler, the former does not recess the boiler barrel for the purpose
of obtaining a low centre. Webb also divides his tubes into two sets by having the
combustion chamber between them. McConnell’s combustion chamber was a
continuation of the fire-box. We must now describe the general appearance of this
engine.

Fig. 64.—McCONNELL’S “300,” LONDON AND NORTH WESTERN

RAILWAY
The cylinders were inclined upwards from the front, and the valve chests were
above them, below the smoke-box. Two Salter safety valves were provided, encased
within a sheet-brass covering of Stirling’s Great Northern pattern. The steam pressure
was 150lbs. The dome was also of brass, with a hemispherical top surmounting the
cylindrical lower part. The steam regulator was at the mouth of the steam-pipe, which
was placed at the top of the dome (inside, of course).
The heating surface was: Tubes, 980 sq. ft.; fire-box, 260 sq. ft. Wheel base, 16ft.
10in. Sufficient steam could be raised in 45 minutes after lighting the fire to move the
engine. Two of these engines were built about the same time—one (No. 300) by
Fairbairn and Co., Manchester, the other by E. B. Wilson and Co., Leeds. The orders
were given early in July, 1852, and the engines delivered the second week in
November, Wilson and Co. having occupied but eight weeks in the construction of the
one given to them.
Both engines were delivered at Wolverton on the same day, and on Thursday,
November 11th, 1852, Wilson’s engine was tried for the first time, when on her first
journey to Euston she attained a speed of 60 miles an hour.
It was soon found that “No. 300” and her sister engine were unable to cover the
111 miles—Euston to Birmingham—in two hours, as was confidently predicted, and
the failure to do so was—perhaps justly—attributed to the inferior condition of the
permanent-way. On March 8th, 1853, “No. 300” hauled a train of 34 carriages,
weighing 170 tons, from Birmingham to London in three hours eight minutes, including
five stoppages. A similar train drawn by the “Heron” and “Prince of Wales” took ten
minutes longer to perform the same journey. These two engines had cylinders 15in. by
20in., and 6ft. driving wheels. The results of this trial are thus tabulated:—
 Coke. Average speed Maximum speed
Coke.
per mile. per hour. per hour.
No. 300 4,529 lb. 40.8 lb. 36.4 miles 54
“Heron” & “Prince of Wales” 4,851 lb. 43.7 lb. 34.5 miles 48

Upon the result of this run it was claimed that McConnell’s patent engines were
considerably superior to two of the ordinary London and North Western Railway
locomotives, and one of Stephenson’s “long boiler” abortions was altered by
McConnell, being fitted up with his patent combustion chamber, short tubes, and the
other innovations, as mentioned in our description of “No. 300.”
The “long boiler” originally had 1,013 sq. ft. of tube-heating surface; when altered,
the length of the tubes was reduced to 4¾ft., and some additional ones were fixed
diagonally across the combustion chamber. By this alteration the tube-heating surface
was reduced to 547 sq. ft., and the engine is stated to have drawn 170 tons at 60
miles an hour, and to have attained a speed of 70 miles an hour with light trains. From
the working of this locomotive the following table (by which a reduction of 23 per cent.
in the amount of fuel consumed was claimed for the altered engine) was prepared:—
Coke
Miles Average Coke Coke
per ton
run. load. consumed. per mile.
per mile.
Original 29,442 115 tons 1,715,952 lb. 58.28 lb. .564 lb.
Altered 12,060 144 tons 519,120 lb. 43.04 lb. .298 lb.

But D. K. Clark’s paper on “Locomotive Boilers,” read before the Institution of Civil
Engineers, soon placed a very different complexion upon the result of the trials
between the ordinary and patent engines, resulting in the “air-tubes” to the combustion
chamber being speedily abandoned. The attention of the directors of the London and
North Western Railway was called to the failure of these engines, with the result that
they ordered Messrs. Marshall and Wood to report on the two classes of engines—
viz., the ordinary London and North Western type and McConnell’s patent
locomotives. This report was ready in August, 1853, but for some reason its
publication was suppressed at the time, but the directors countermanded the
construction of other engines already ordered on McDonnell’s patent principle.
In the summer of 1854 Marshall and Wood conducted another set of experiments
for the directors of the London and North Western Railway, with the object of
determining the relative value of coke and coal as fuel for the locomotives.
The engines chosen were McConnell’s patent “No. 303” and the “Bloomer,” No.
293. Double trips were run between Rugby and London daily for six consecutive days,
coal being burnt on three days and coke on the three alternate days. The trains
chosen were the 12.55 p.m. up and 5.45 p.m. down.
It was found that 1lb. of coal evaporated 5.83lb. of water, and 1lb. of coke 8.65lb.
of water; but the monetary saving was 6s. 9d. per ton in favour of coal.
McConnell’s patent engines were again condemned. Marshall and Wood’s report
concluded as follows: “Although we consider the experiments we made with No. 303
engine satisfactory in point of smoke burning, we cannot resist the belief that the
consumption of coal is in excess of what it ought to be, and that there is room for
considerable improvement in this respect, by means which shall tend to utilise the
heat which is at present wasted.”
The whole report is of great interest to the technical reader; it is, however, too long
to reproduce in extenso.
It is abundantly evident that there is no great pecuniary gain from locomotive
designing, or we should be treated to great law-suits regarding the validity of the
patents, such as have recently been the case with pneumatic tyres and incandescent
gas-burners. We have already, upon more occasions than one, pointed out that certain
patented locomotive designs had previously been anticipated, although the later
patentees were probably unaware of the fact. We find this to have been the case with
McConnell’s “recessed” boiler locomotives just described, for on December 2nd, 1846,
W. Stubbs and J. J. Grylls, of Llanelly, enrolled a design of locomotive. The
specification in question not only mentioned the recessing of the boiler for the purpose
of allowing the use of a large driving wheel and yet retaining a low centre of gravity,
but it even anticipated McConnell’s combustion chamber between the fire-box and
tubes. An adaptation of Bodmer’s double piston motion was also specified by Stubbs
and Grylls. The two cylinders were placed below the boiler, four wheels being
connected by means of side-rods with the cross-heads of the two cylinders in such a
manner that from each cylinder two wheels were driven, by means of a cross-head,
and each cross-head, by means of two connecting-rods, rotating the wheels. Another
claim under this patent related to driving a locomotive by eccentrics fitted with
antifriction rollers as a substitute for the ordinary cranks.
Although in the “Evolution of the Steam Locomotive” it is only intended to describe
locomotives for British railways, it may not be out of place to mention an engine for a
foreign railway, for two reasons—first, because it was built by an English firm in
England, and, secondly, because it was tried on an English railway before exportation.
The “Ysabel” was constructed in 1853 by Dodds and Sons, of Rotherham, for the
“Railway of Isabella II. from Santander to Abar del Rey,” and was tried on the Lickey
incline of 1 in 37 for two miles, under the direction of Mr. Stalvies, the locomotive
superintendent at Broomsgrove. The “Ysabel” had four-coupled wheels 4ft. 6in.
diameter; cylinders, 14¼in. by 20in. stroke; 137 tubes, 1⅞in. diameter, and 11ft. 3in. in
length, and was fitted with Dodds’ patent wedge expansive motion, which required
only two eccentrics. For the purpose of easy transportation, the “Ysabel” was so
constructed that when disconnected no single portion weighed more than six tons; in
addition to the fittings necessary to secure the boiler, the only connections between it
and the frames, machinery, etc., were the steam-pipe and the two feed-pump
connections. When tried upon the Lickey bank this locomotive hauled six trucks
weighing 45 tons 12¾ cwt. up the two miles one furlong in 12 minutes 12 seconds,
and with a train weighing 29 tons 4¼ cwt. the incline was negotiated in seven minutes
five seconds.
The compound locomotive is not quite so modern an invention as is popularly
supposed, for, putting aside the suggestion emanating in 1850 from John Nicholson,
an Eastern Counties Railway engine-driver, whose plan of continuous expansion is
generally accepted as the foundation of the compound system, we find that in 1853 a
Mr. Edwards, of Birmingham, patented a “duplex” or in other words a compound
engine, the steam, after working in a high-pressure cylinder, being used over again in
a low-pressure one. The cylinders were so placed that the dead centre in one
occurred when the other piston was at its maximum power.
In 1853 Beattie constructed for the London and South Western Railway at Nine
Elms Works, the “Duke,” No. 123, a six-wheel “single” express engine; driving wheels,
6ft. 6in. diameter; L. and T. 3ft. 6in. diameter; cylinders, 16in. by 21in. stroke. The
weight was arranged in an extraordinary manner, 10 tons 9 cwt. being on the leading
axle, only 9 tons 9 cwt. on the driving axle, and 5 tons 11 cwt. on the trailing axle. The
wheel base was, L. to D., 6ft. 8½in.; D. to T., 7ft. 6in. The “Duke” had a raised fire-box,
surmounted by a large dome similar to that of the “Hercules,” whilst another dome was
located on the centre of the boiler barrel. The shape of this centre dome resembled a
soup-tureen turned upside down.
At this point we take the opportunity to briefly describe a railway locomotive which,
although not propelled by steam, deserves to be mentioned as an initial attempt at
railway haulage by means of compressed air.
The engine in question was constructed by Arthur Pasey, and was tried on the
Eastern Counties Railway in July, 1852. This machine was, in point of size and power,
nothing more than a model, the dimensions being: Cylinders, 2½in. diameter, 9in.
stroke; driving wheels, 4ft. diameter; weight, 1½ tons; air capacity of reservoirs, 39
cubic ft.

Fig. 65.—PASEY’S COMPRESSED AIR LOCOMOTIVE, TRIED ON

THE EASTERN COUNTIES RAILWAY IN 1852
By reference to the illustration (Fig. 65) it will be seen that this curious little
locomotive had the six wheels of 4ft. diameter within the frames, and the horizontal
cylinders outside the frames, and actuating the centre pair of wheels. Above the
frames was placed a cylindrical air reservoir, with egg shaped ends. This extended
from the buffer beam at one end of the vehicle to the leading axle, a distance of about
12ft. The remainder of the space, about 4ft., was occupied by the pressure-reducing
and other apparatus, and afforded a place of vantage for those in charge of the
machine. The reservoir was constructed to withstand a pressure of 200lb., but the
engine was only pressed to 165lb., and this at the time of the trial at Stratford was