Molecular machine

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Molecular_machine

A molecular machine, nanite, or nanomachine, is a molecular component that produces quasi-mechanical movements (output) in response to specific stimuli (input). In biology, macromolecular machines frequently perform tasks essential for life such as DNA replication and ATP synthesis. The expression is often more generally applied to molecules that simply mimic functions that occur at the macroscopic level. The term is also common in nanotechnology where a number of highly complex molecular machines have been proposed that are aimed at the goal of constructing a molecular assembler.

Kinesin walking on a microtubule is a molecular biological machine using protein domain dynamics on nanoscales

For the last several decades, chemists and physicists alike have attempted, with varying degrees of success, to miniaturize machines found in the macroscopic world. Molecular machines research is currently at the forefront with the 2016 Nobel Prize in Chemistry being awarded to Jean-Pierre Sauvage, Sir J. Fraser Stoddart and Bernard L. Feringa for the design and synthesis of molecular machines.

Types

Molecular machines can be divided into two broad categories; artificial and biological. In general, artificial molecular machines (AMMs) refer to molecules that are artificially designed and synthesized whereas biological molecular machines can commonly be found in nature and have evolved into their forms after abiogenesis on Earth.

Artificial

A wide variety of artificial molecular machines (AMMs) have been synthesized by chemists which are rather simple and small compared to biological molecular machines. The first AMM, a molecular shuttle, was synthesized by Sir J. Fraser Stoddart. A molecular shuttle is a rotaxane molecule where a ring is mechanically interlocked onto an axle with two bulky stoppers. The ring can move between two binding sites with various stimuli such as light, pH, solvents, and ions. As the authors of this 1991 JACS paper noted: “Insofar as it becomes possible to control the movement of one molecular component with respect to the other in a [2]rotaxane, the technology for building molecular machines will emerge.”, mechanically interlocked molecular architectures spearheaded AMM design and synthesis as they provide directed molecular motion. Today a wide variety of AMMs exists as listed below.

Overcrowded alkane molecular motor.

Molecular motors

Molecular motors are molecules that are capable of rotary motion around a single or double bond.

Single bond rotary motors  are generally fueled by chemical reactions whereas double bond rotary motors  are generally fueled by light. The rotation speed of the motor can also be tuned by careful molecular design. Carbon nanotube nanomotors have also been produced.

Molecular propeller

A molecular propeller is a molecule that can propel fluids when rotated, due to its special shape that is designed in analogy to macroscopic propellers. It has several molecular-scale blades attached at a certain pitch angle around the circumference of a nanoscale shaft. Also see molecular gyroscope.

Daisy chain [2]rotaxane. These molecules are considered as building blocks for artificial muscle.

Molecular switch

A molecular switch is a molecule that can be reversibly shifted between two or more stable states. The molecules may be shifted between the states in response to changes in pH, light, temperature, an electric current, microenvironment, or the presence of a ligand.

Rotaxane based molecular shuttle.

Molecular shuttle

A molecular shuttle is a molecule capable of shuttling molecules or ions from one location to another. A common molecular shuttle consists of a rotaxane where the macrocycle can move between two sites or stations along the dumbbell backbone.

Nanocar

Nanocars are single molecule vehicles that resemble macroscopic automobiles and are important for understanding how to control molecular diffusion on surfaces. The first nanocars were synthesized by James M. Tour in 2005. They had an H shaped chassis and 4 molecular wheels (fullerenes) attached to the four corners. In 2011, Ben Feringa and co-workers synthesized the first motorized nanocar which had molecular motors attached to the chassis as rotating wheels. The authors were able to demonstrate directional motion of the nanocar on a copper surface by providing energy from a scanning tunneling microscope tip. Later, in 2017, the world's first ever Nanocar Race took place in Toulouse.

Molecular balance

A molecular balance is a molecule that can interconvert between two and more conformational or configurational states in response to the dynamic of multiple intra- and intermolecular driving forces, such as hydrogen bonding, solvophobic/hydrophobic effects, π interactions, and steric and dispersion interactions. Molecular balances can be small molecules or macromolecules such as proteins. Cooperatively folded proteins, for example, have been used as molecular balances to measure interaction energies and conformational propensities.

Molecular tweezers

Molecular tweezers are host molecules capable of holding items between their two arms. The open cavity of the molecular tweezers binds items using non-covalent bonding including hydrogen bonding, metal coordination, hydrophobic forces, van der Waals forces, π interactions, or electrostatic effects. 

Examples of molecular tweezers have been reported that are constructed from DNA and are considered DNA machines.

Molecular sensor

A molecular sensor is a molecule that interacts with an analyte to produce a detectable change.

 Molecular sensors combine molecular recognition with some form of reporter, so the presence of the item can be observed.

Molecular logic gate

A molecular logic gate is a molecule that performs a logical operation on one or more logic inputs and produces a single logic output. Unlike a molecular sensor, the molecular logic gate will only output when a particular combination of inputs are present.

Molecular assembler

A molecular assembler is a molecular machine able to guide chemical reactions by positioning reactive molecules with precision.

Molecular hinge

A molecular hinge is a molecule that can be selectively switched from one configuration to another in a reversible fashion. Such configurations must have distinguishable geometries, for instance, Cis or Trans isomers of a V-shape molecule. Azo compounds perform Cis–trans isomerism upon receiving UV-Vis light.

Biological

A ribosome translating a protein

The most complex macromolecular machines are found within cells, often in the form of multi-protein complexes. Some biological machines are motor proteins, such as myosin, which is responsible for muscle contraction, kinesin, which moves cargo inside cells away from the nucleus along microtubules, and dynein, which moves cargo inside cells towards the nucleus and produces the axonemal beating of motile cilia and flagella. "[I]n effect, the [motile cilium] is a nanomachine composed of perhaps over 600 proteins in molecular complexes, many of which also function independently as nanomachines ...  

Flexible linkers allow the mobile protein domains connected by them to recruit their binding partners and induce long-range allostery via protein domain dynamics." Other biological machines are responsible for energy production, for example ATP synthase which harnesses energy from proton gradients across membranes to drive a turbine-like motion used to synthesise ATP, the energy currency of a cell. Still other machines are responsible for gene expression, including DNA polymerases for replicating DNA, RNA polymerases for producing mRNA, the spliceosome for removing introns, and the ribosome for synthesising proteins. These machines and their nanoscale dynamics are far more complex than any molecular machines that have yet been artificially constructed.

Some biological molecular machines

These biological machines might have applications in nanomedicine. For example, they could be used to identify and destroy cancer cells. Molecular nanotechnology is a speculative subfield of nanotechnology regarding the possibility of engineering molecular assemblers, biological machines which could re-order matter at a molecular or atomic scale. Nanomedicine would make use of these nanorobots, introduced into the body, to repair or detect damages and infections. Molecular nanotechnology is highly theoretical, seeking to anticipate what inventions nanotechnology might yield and to propose an agenda for future inquiry. The proposed elements of molecular nanotechnology, such as molecular assemblers and nanorobots are far beyond current capabilities.

Research

The construction of more complex molecular machines is an active area of theoretical and experimental research. A number of molecules, such as molecular propellers, have been designed, although experimental studies of these molecules are inhibited by the lack of methods to construct these molecules. In this context, theoretical modeling can be extremely useful to understand the self-assembly/disassembly processes of rotaxanes, important for the construction of light-powered molecular machines. This molecular-level knowledge may foster the realization of ever more complex, versatile, and effective molecular machines for the areas of nanotechnology, including molecular assemblers.

Although currently not feasible, some potential applications of molecular machines are transport at the molecular level, manipulation of nanostructures and chemical systems, high density solid-state informational processing and molecular prosthetics. Many fundamental challenges need to be overcome before molecular machines can be used practically such as autonomous operation, complexity of machines, stability in the synthesis of the machines and the working conditions.

Biorobotics

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Biorobotics 

 

Biorobotics is an interdisciplinary science that combines the fields of biomedical engineering, cybernetics, and robotics to develop new technologies that integrate biology with mechanical systems to develop more efficient communication, alter genetic information, and create machines that imitate biological systems.

Cybernetics

Cybernetics focuses on the communication and system of living organisms and machines that can be applied and combined with multiple fields of study such as biology, mathematics, computer science, engineering, and much more.

This discipline falls under the branch of biorobotics because of its combined field of study between biological bodies and mechanical systems. Studying these two systems allow for advanced analysis on the functions and processes of each system as well as the interactions between them.

History

Cybernetic theory is a concept that has existed for centuries, dating back to the era of Plato where he applied the term to refer to the “governance of people”. The term ‘cybernetique’ is seen in the mid 1800s used by physicist André-Marie Ampère. The term “cybernetics” was popularized in the late 1940s to refer to a discipline that touched on, but was separate, from established disciplines, such as electrical engineering, mathematics, and biology.

Science

Cybernetics is often misunderstood because of the breadth of disciplines it covers. In the early 20th century, it was coined as an interdisciplinary field of study that combines biology, science, network theory, and engineering. Today, it covers all scientific fields with system related processes. The goal of cybernetics is to analyze systems and processes of any system or systems in an attempt to make them more efficient and effective.

Applications

Cybernetics is used as an umbrella term so applications extend to all systems related scientific fields such as biology, mathematics, computer science, engineering, management, psychology, sociology, art, and more. Cybernetics is used amongst several fields to discover principles of systems, adaptation of organisms, information analysis and much more.

Genetic Engineering

Genetic engineering is a field that uses advances in technology to modify biological organisms. Through different methods, scientists are able to alter the genetic material of microorganisms, plants and animals to provide them with desirable traits. Genetic engineering is included in biorobotics because it uses new technologies to alter biology and change an organism's DNA for their and society's benefit.

History

Although humans have been modifying genetic material of animals and plants through artificial selection for millennia (such as the genetic mutations that developed teosinte into corn and wolves into dogs), genetic engineering refers to the deliberate alteration or insertion of specific genes to an organism's DNA. The first successful case of genetic engineering occurred in 1973 when Herbert Boyer and Stanley Cohen were able to transfer a gene with antibiotic resistance to a bacteria.

Science

There are three main techniques used in genetic engineering: The plasmid method, the vector method and the biolistic method.

Plasmid Method

This technique is used mainly for microorganisms such as bacteria. Through this method, DNA molecules called plasmids are extracted from bacteria and placed in a lab where restriction enzymes break them down. As the enzymes break the molecules down, some develop a rough edge that resembles that of a staircase which is considered ‘sticky’ and capable of reconnecting. These ‘sticky’ molecules are inserted into another bacteria where they will connect to the DNA rings with the altered genetic material.

Vector Method

The vector method is considered a more precise technique than the plasmid method as it involves the transfer of a specific gene instead of a whole sequence. In the vector method, a specific gene from a DNA strand is isolated through restriction enzymes in a laboratory and is inserted into a vector. Once the vector accepts the genetic code, it is inserted into the host cell where the DNA will be transferred.

Biolistic Method

The biolistic method is typically used to alter the genetic material of plants. This method embeds the desired DNA with a metallic particle such as gold or tungsten in a high speed gun. The particle is then bombarded into the plant. Due to the high velocities and the vacuum generated during bombardment, the particle is able to penetrate the cell wall and inserts the new DNA into the cell.

Applications

Genetic engineering has many uses in the fields of medicine, research and agriculture. In the medical field, genetically modified bacteria are used to produce drugs such as insulin, human growth hormones and vaccines. In research, scientists genetically modify organisms to observe physical and behavioral changes to understand the function of specific genes. In agriculture, genetic engineering is extremely important as it is used by farmers to grow crops that are resistant to herbicides and to insects such as BTCorn.

Bionics

Bionics is a medical engineering field and a branch of biorobotics consisting of electrical and mechanical systems that imitate biological systems, such as prosthetics and hearing aids. It's a portmanteau that combines biology and electronics.

History

The history of bionics goes as far back in time as ancient Egypt. A prosthetic toe made out of wood and leather was found on the foot of a mummy. The time period of the mummy corpse was estimated to be from around the fifteenth century B.C. Bionics can also be witnessed in ancient Greece and Rome. Prosthetic legs and arms were made for amputee soldiers. In the early 16th century, a French military surgeon by the name of Ambroise Pare became a pioneer in the field of bionics. He was known for making various types of upper and lower prosthetics. One of his most famous prosthetics, Le Petit Lorrain, was a mechanical hand operated by catches and springs. During the early 19th century, Alessandro Volta further progressed bionics. He set the foundation for the creation of hearing aids with his experiments. He found that electrical stimulation could restore hearing by inserting an electrical implant to the saccular nerve of a patient's ear. In 1945, the National Academy of Sciences created the Artificial Limb Program, which focused on improving prosthetics since there were a large number of World War II amputee soldiers. Since this creation, prosthetic materials, computer design methods, and surgical procedures have improved, creating modern-day bionics.

Science

Prosthetics

The important components that make up modern-day prosthetics are the pylon, the socket, and the suspension system. The pylon is the internal frame of the prosthetic that is made up of metal rods or carbon-fiber composites. The socket is the part of the prosthetic that connects the prosthetic to the person's missing limb. The socket consists of a soft liner that makes the fit comfortable, but also snug enough to stay on the limb. The suspension system is important in keeping the prosthetic on the limb. The suspension system is usually a harness system made up of straps, belts or sleeves that are used to keep the limb attached.

The operation of a prosthetic could be designed in various ways. The prosthetic could be body-powered, externally-powered, or myoelectrically-powered. Body-powered prosthetics consist of cables attached to a strap or harness, which is placed on the person's functional shoulder, allowing the person to manipulate and control the prosthetic as he or she deems fit. Externally-powered prosthetics consist of motors to power the prosthetic and buttons and switches to control the prosthetic. Myoelectrically-powered prosthetics are new, advanced forms of prosthetics where electrodes are placed on the muscles above the limb. The electrodes will detect the muscle contractions and send electrical signals to the prosthetic to move the prosthetic.

Hearing Aids

Four major components make up the hearing aid: the microphone, the amplifier, the receiver, and the battery. The microphone takes in outside sound, turns that sound to electrical signals, and sends those signals to the amplifier. The amplifier increases the sound and sends that sound to the receiver. The receiver changes the electrical signal back into sound and sends the sound into the ear. Hair cells in the ear will sense the vibrations from the sound, convert the vibrations into nerve signals, and send it to the brain so the sounds can become coherent to the person. The battery simply powers the hearing aid.

Applications

Cochlear Implant

Cochlear implants are a type of hearing aid for those who are deaf. Cochlear implants send electrical signals straight to the auditory nerve, the nerve responsible for sound signals, instead of just sending the signals to the ear canal like normal hearing aids.

New Bone-Anchored (Baha) Hearing Aids

These hearing aids are also used for people with severe hearing loss. Baha hearing aids attach to the bones of the middle ear to create the sound vibrations in the skull and send those vibrations to the cochlea.

Artificial Sensing Skin

This artificial sensing skin detects any pressure put on it and is meant for people who have lost any sense of feeling on parts of their bodies, such as diabetics with peripheral neuropathy.

Bionic Eye

The bionic eye is a bioelectronic implant that restores vision for people with blindness.

Orthopedic Bionics

Orthopedic bionics consist of advanced bionic limbs that use a person's neuromuscular system to control the bionic limb.

Endoscopic Robotics

These robotics can remove a polyp during a colonoscopy.

Brain-reading

From Wikipedia, the free encyclopedia

Brain-reading or thought identification uses the responses of multiple voxels in the brain evoked by stimulus then detected by fMRI in order to decode the original stimulus. Advances in research have made this possible by using human neuroimaging to decode a person's conscious experience based on non-invasive measurements of an individual's brain activity.^[1] Brain reading studies differ in the type of decoding (i.e. classification, identification and reconstruction) employed, the target (i.e. decoding visual patterns, auditory patterns, cognitive states), and the decoding algorithms (linear classification, nonlinear classification, direct reconstruction, Bayesian reconstruction, etc.) employed.

Professor of neuropsychology Barbara Sahakian qualifies, "A lot of neuroscientists in the field are very cautious and say we can't talk about reading individuals' minds, and right now that is very true, but we're moving ahead so rapidly, it's not going to be that long before we will be able to tell whether someone's making up a story, or whether someone intended to do a crime with a certain degree of certainty."

Applications

Natural images

Identification of complex natural images is possible using voxels from early and anterior visual cortex areas forward of them (visual areas V3A, V3B, V4, and the lateral occipital) together with Bayesian inference. This brain reading approach uses three components: a structural encoding model that characterizes responses in early visual areas; a semantic encoding model that characterizes responses in anterior visual areas; and a Bayesian prior that describes the distribution of structural and semantic scene statistics.

Experimentally the procedure is for subjects to view 1750 black and white natural images that are correlated with voxel activation in their brains. Then subjects viewed another 120 novel target images, and information from the earlier scans is used reconstruct them. Natural images used include pictures of a seaside cafe and harbor, performers on a stage, and dense foliage.

In 2008 IBM applied for a patent on how to extract mental images of human faces from the human brain. It uses a feedback loop based on brain measurements of the fusiform gyrus area in the brain which activates proportionate with degree of facial recognition.

In 2011, a team led by Shinji Nishimoto used only brain recordings to partially reconstruct what volunteers were seeing. The researchers applied a new model, about how moving object information is processed in human brains, while volunteers watched clips from several videos. An algorithm searched through thousands of hours of external YouTube video footage (none of the videos were the same as the ones the volunteers watched) to select the clips that were most similar. The authors have uploaded demos comparing the watched and the computer-estimated videos.

Lie detector

Brain-reading has been suggested as an alternative to polygraph machines as a form of lie detection.her alternative to polygraph machines is blood oxygenated level dependent functional MRI technology (BOLD fMRI). This technique involves the interpretation of the local change in the concentration of oxygenated hemoglobin in the brain, although the relationship between this blood flow and neural activity is not yet completely understood. Another technique to find concealed information is brain fingerprinting, which uses EEG to ascertain if a person has a specific memory or information by identifying P300 event related potentials.

A number of concerns have been raised about the accuracy and ethical implications of brain-reading for this purpose. Laboratory studies have found rates of accuracy of up to 85%; however, there are concerns about what this means for false positive results among non-criminal populations: "If the prevalence of "prevaricators" in the group being examined is low, the test will yield far more false-positive than true-positive results; about one person in five will be incorrectly identified by the test." Ethical problems involved in the use of brain-reading as lie detection include misapplications due to adoption of the technology before its reliability and validity can be properly assessed and due to misunderstanding of the technology, and privacy concerns due to unprecedented access to individual's private thoughts. However, it has been noted that the use of polygraph lie detection carries similar concerns about the reliability of the results and violation of privacy.

Human-machine interfaces

The Emotiv Epoc is one way that users can give commands to devices using only thoughts

Brain-reading has also been proposed as a method of improving human-machine interfaces, by the use of EEG to detect relevant brain states of a human. In recent years, there has been a rapid increase in patents for technology involved in reading brainwaves, rising from fewer than 400 from 2009–2012 to 1600 in 2014. These include proposed ways to control video games via brain waves and "neuro-marketing" to determine someone's thoughts about a new product or advertisement.

Emotiv Systems, an Australian electronics company, has demonstrated a headset that can be trained to recognize a user's thought patterns for different commands. Tan Le demonstrated the headset's ability to manipulate virtual objects on screen, and discussed various future applications for such brain-computer interface devices, from powering wheel chairs to replacing the mouse and keyboard.

Detecting attention

It is possible to track which of two forms of rivalrous binocular illusions a person was subjectively experiencing from fMRI signals.

When humans think of an object, such as a screwdriver, many different areas of the brain activate. Marcel Just and his colleague, Tom Mitchell, have used fMRI brain scans to teach a computer to identify the various parts of the brain associated with specific thoughts. This technology also yielded a discovery: similar thoughts in different human brains are surprisingly similar neurologically. To illustrate this, Just and Mitchell used their computer to predict, based on nothing but fMRI data, which of several images a volunteer was thinking about. The computer was 100% accurate, but so far the machine is only distinguishing between 10 images.

Detecting thoughts

The category of event which a person freely recalls can be identified from fMRI before they say what they remembered.

December 16, 2015, a study conducted by Toshimasa Yamazaki at Kyushu Institute of Technology found that during a rock-paper-scissors game a computer was able to determine the choice made by the subjects before they moved their hand. An EEG was used to measure activity in the Broca's area to see the words two seconds before the words were uttered.

Detecting language

Statistical analysis of EEG brainwaves has been claimed to allow the recognition of phonemes, and at a 60% to 75% level color and visual shape words.

On 31 January 2012 Brian Pasley and colleagues of University of California Berkeley published their paper in PLoS Biology wherein subjects' internal neural processing of auditory information was decoded and reconstructed as sound on computer by gathering and analyzing electrical signals directly from subjects' brains. The research team conducted their studies on the superior temporal gyrus, a region of the brain that is involved in higher order neural processing to make semantic sense from auditory information. The research team used a computer model to analyze various parts of the brain that might be involved in neural firing while processing auditory signals. Using the computational model, scientists were able to identify the brain activity involved in processing auditory information when subjects were presented with recording of individual words. Later, the computer model of auditory information processing was used to reconstruct some of the words back into sound based on the neural processing of the subjects. However the reconstructed sounds were not of good quality and could be recognized only when the audio wave patterns of the reconstructed sound were visually matched with the audio wave patterns of the original sound that was presented to the subjects. However this research marks a direction towards more precise identification of neural activity in cognition.

Predicting intentions

Some researchers in 2008 were able to predict, with 60% accuracy, whether a subject was going to push a button with their left or right hand. This is notable, not just because the accuracy is better than chance, but also because the scientists were able to make these predictions up to 10 seconds before the subject acted – well before the subject felt they had decided. This data is even more striking in light of other research suggesting that the decision to move, and possibly the ability to cancel that movement at the last second, may be the results of unconscious processing.^[27]

John Dylan-Haynes has also demonstrated that fMRI can be used to identify whether a volunteer is about to add or subtract two numbers in their head.

Predictive processing in the brain

Neural decoding techniques have been used to test theories about the predictive brain, and to investigate how top-down predictions affect brain areas such as the visual cortex. Studies using fMRI decoding techniques have found that predictable sensory events and the expected consequences of our actions are better decoded in visual brain areas, suggesting that prediction 'sharpens' representations in line with expectations.

Virtual environments

It has also been shown that brain-reading can be achieved in a complex virtual environment.

Emotions

Just and Mitchell also claim they are beginning to be able to identify kindness, hypocrisy, and love in the brain.

Security

In 2013 a project led by University of California Berkeley professor John Chuang published findings on the feasibility of brainwave-based computer authentication as a substitute for passwords. Improvements in the use of biometrics for computer authentication has continually improved since the 1980s, but this research team was looking for a method faster and less intrusive than today's retina scans, fingerprinting, and voice recognition. The technology chosen to improve security measures is an electroencephalogram (EEG), or brainwave measurer, to improve passwords into "pass thoughts." Using this method Chuang and his team were able to customize tasks and their authentication thresholds to the point where they were able to reduce error rates under 1%, significantly better than other recent methods. In order to better attract users to this new form of security the team is still researching mental tasks that are enjoyable for the user to perform while having their brainwaves identified. In the future this method could be as cheap, accessible, and straightforward as thought itself.

John-Dylan Haynes states that fMRI can also be used to identify recognition in the brain. He provides the example of a criminal being interrogated about whether he recognizes the scene of the crime or murder weapons.

Methods of analysis

Classification

In classification, a pattern of activity across multiple voxels is used to determine the particular class from which the stimulus was drawn. Many studies have classified visual stimuli, but this approach has also been used to classify cognitive states.

Reconstruction

In reconstruction brain reading the aim is to create a literal picture of the image that was presented. Early studies used voxels from early visual cortex areas (V1, V2, and V3) to reconstruct geometric stimuli made up of flickering checkerboard patterns.

EEG

EEG has also been used to identify recognition of specific information or memories by the P300 event related potential, which has been dubbed 'brain fingerprinting'.

Accuracy

Brain-reading accuracy is increasing steadily as the quality of the data and the complexity of the decoding algorithms improve. In one recent experiment it was possible to identify which single image was being seen from a set of 120. In another it was possible to correctly identify 90% of the time which of two categories the stimulus came and the specific semantic category (out of 23) of the target image 40% of the time.

Limitations

It has been noted that so far brain-reading is limited. "In practice, exact reconstructions are impossible to achieve by any reconstruction algorithm on the basis of brain activity signals acquired by fMRI. This is because all reconstructions will inevitably be limited by inaccuracies in the encoding models and noise in the measured signals. Our results demonstrate that the natural image prior is a powerful (if unconventional) tool for mitigating the effects of these fundamental limitations. A natural image prior with only six million images is sufficient to produce reconstructions that are structurally and semantically similar to a target image."

Ethical issues

With brain scanning technology becoming increasingly accurate, experts predict important debates over how and when it should be used. One potential area of application is criminal law. Haynes states that simply refusing to use brain scans on suspects also prevents the wrongly accused from proving their innocence. US scholars generally believe that involuntary brain reading, and involuntary polygraph tests, would violate the 5th Amendment's right to not self incriminate. One perspective is to consider whether brain imaging is like testimony, or instead like DNA, blood, or semen. Paul Root Wolpe, director of the Center for Ethics at Emory University in Atlanta predicts that this question will be decided by a Supreme Court case.

In other countries outside the United States, thought identification has already been used in criminal law. In 2008 an Indian woman was convicted of murder after an EEG of her brain allegedly revealed that she was familiar with the circumstances surrounding the poisoning of her ex-fiancé. Some neuroscientists and legal scholars doubt the validity of using thought identification as a whole for anything past research on the nature of deception and the brain.

The Economist cautioned people to be "afraid" of the future impact, and some ethicists argue that privacy laws should protect private thoughts. Legal scholar Hank Greely argues that the court systems could benefit from such technology, and neuroethicist Julian Savulescu states that brain data is not fundamentally different from other types of evidence. In Nature, journalist Liam Drew writes about emerging projects to attach brain-reading devices to speech synthesizers or other output devices for the benefit of tetraplegics. Such devices could create concerns of accidentally broadcasting the patient's "inner thoughts" rather than merely conscious speech.

History

MRI scanner that could be used for Thought Identification

Psychologist John-Dylan Haynes experienced breakthroughs in brain imaging research in 2006 by using fMRI. This research included new findings on visual object recognition, tracking dynamic mental processes, lie detecting, and decoding unconscious processing. The combination of these four discoveries revealed such a significant amount of information about an individual's thoughts that Haynes termed it "brain reading".

The fMRI has allowed research to expand by significant amounts because it can track the activity in an individual's brain by measuring the brain's blood flow. It is currently thought to be the best method for measuring brain activity, which is why it has been used in multiple research experiments in order to improve the understanding of how doctors and psychologists can identify thoughts.

In a 2020 study, AI using implanted electrodes could correctly transcribe a sentence read aloud from a fifty-sentence test set 97% of the time, given 40 minutes of training data per participant.

Future research

Experts are unsure of how far thought identification can expand, but Marcel Just believed in 2014 that in 3–5 years there will be a machine that is able to read complex thoughts such as 'I hate so-and-so'.

Donald Marks, founder and chief science officer of MMT, is working on playing back thoughts individuals have after they have already been recorded.

Researchers at the University of California Berkeley have already been successful in forming, erasing, and reactivating memories in rats. Marks says they are working on applying the same techniques to humans. This discovery could be monumental for war veterans who suffer from PTSD.

Further research is also being done in analyzing brain activity during video games to detect criminals, neuromarketing, and using brain scans in government security checks.

Neuroprosthetics

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Neuroprosthetics

Neuroprosthetics (also called neural prosthetics) is a discipline related to neuroscience and biomedical engineering concerned with developing neural prostheses. They are sometimes contrasted with a brain–computer interface, which connects the brain to a computer rather than a device meant to replace missing biological functionality.

Neural prostheses are a series of devices that can substitute a motor, sensory or cognitive modality that might have been damaged as a result of an injury or a disease. Cochlear implants provide an example of such devices. These devices substitute the functions performed by the eardrum and stapes while simulating the frequency analysis performed in the cochlea. A microphone on an external unit gathers the sound and processes it; the processed signal is then transferred to an implanted unit that stimulates the auditory nerve through a microelectrode array. Through the replacement or augmentation of damaged senses, these devices intend to improve the quality of life for those with disabilities.

These implantable devices are also commonly used in animal experimentation as a tool to aid neuroscientists in developing a greater understanding of the brain and its functioning. By wirelessly monitoring the brain's electrical signals sent out by electrodes implanted in the subject's brain, the subject can be studied without the device affecting the results.

Accurately probing and recording the electrical signals in the brain would help better understand the relationship among a local population of neurons that are responsible for a specific function.

Neural implants are designed to be as small as possible in order to be minimally invasive, particularly in areas surrounding the brain, eyes or cochlea. These implants typically communicate with their prosthetic counterparts wirelessly. Additionally, power is currently received through wireless power transmission through the skin. The tissue surrounding the implant is usually highly sensitive to temperature rise, meaning that power consumption must be minimal in order to prevent tissue damage.

The neuroprosthetic currently undergoing the most widespread use is the cochlear implant, with over 300,000 in use worldwide as of 2012.

History

The first known cochlear implant was created in 1957. Other milestones include the first motor prosthesis for foot drop in hemiplegia in 1961, the first auditory brainstem implant in 1977 and a peripheral nerve bridge implanted into the spinal cord of an adult rat in 1981. In 1988, the lumbar anterior root implant and functional electrical stimulation (FES) facilitated standing and walking, respectively, for a group of paraplegics.

Regarding the development of electrodes implanted in the brain, an early difficulty was reliably locating the electrodes, originally done by inserting the electrodes with needles and breaking off the needles at the desired depth. Recent systems utilize more advanced probes, such as those used in deep brain stimulation to alleviate the symptoms of Parkinson's disease. The problem with either approach is that the brain floats free in the skull while the probe does not, and relatively minor impacts, such as a low speed car accident, are potentially damaging. Some researchers, such as Kensall Wise at the University of Michigan, have proposed tethering 'electrodes to be mounted on the exterior surface of the brain' to the inner surface of the skull. However, even if successful, tethering would not resolve the problem in devices meant to be inserted deep into the brain, such as in the case of deep brain stimulation (DBS).

Visual prosthetics

A visual prosthesis can create a sense of image by electrically stimulating neurons in the visual system. A camera would wirelessly transmit to an implant, the implant would map the image across an array of electrodes. The array of electrodes has to effectively stimulate 600-1000 locations, stimulating these optic neurons in the retina thus will create an image. The stimulation can also be done anywhere along the optic signal's path way. The optical nerve can be stimulated in order to create an image, or the visual cortex can be stimulated, although clinical tests have proven most successful for retinal implants.

A visual prosthesis system consists of an external (or implantable) imaging system which acquires and processes the video. Power and data will be transmitted to the implant wirelessly by the external unit. The implant uses the received power/data to convert the digital data to an analog output which will be delivered to the nerve via micro electrodes.

Photoreceptors are the specialized neurons that convert photons into electrical signals. They are part of the retina, a multilayer neural structure about 200 um thick that lines the back of the eye. The processed signal is sent to the brain through the optical nerve. If any part of this pathway is damaged blindness can occur.

Blindness can result from damage to the optical pathway (cornea, aqueous humor, crystalline lens, and vitreous). This can happen as a result of accident or disease. The two most common retinal degenerative diseases that result in blindness secondary to photoreceptor loss is age related macular degeneration (AMD) and retinitis pigmentosa (RP).

The first clinical trial of a permanently implanted retinal prosthesis was a device with a passive microphotodiode array with 3500 elements. This trial was implemented at Optobionics, Inc., in 2000. In 2002, Second Sight Medical Products, Inc. (Sylmar, CA) began a trial with a prototype epiretinal implant with 16 electrodes. The subjects were six individuals with bare light perception secondary to RP. The subjects demonstrated their ability to distinguish between three common objects (plate, cup, and knife) at levels statistically above chance. An active sub retinal device developed by Retina Implant GMbH (Reutlingen, Germany) began clinical trials in 2006. An IC with 1500 microphotodiodes was implanted under the retina. The microphotodiodes serve to modulate current pulses based on the amount of light incident on the photo diode.

The seminal experimental work towards the development of visual prostheses was done by cortical stimulation using a grid of large surface electrodes. In 1968 Giles Brindley implanted an 80 electrode device on the visual cortical surface of a 52-year-old blind woman. As a result of the stimulation the patient was able to see phosphenes in 40 different positions of the visual field. This experiment showed that an implanted electrical stimulator device could restore some degree of vision. Recent efforts in visual cortex prosthesis have evaluated efficacy of visual cortex stimulation in a non-human primate. In this experiment after a training and mapping process the monkey is able to perform the same visual saccade task with both light and electrical stimulation.

The requirements for a high resolution retinal prosthesis should follow from the needs and desires of blind individuals who will benefit from the device. Interactions with these patients indicate that mobility without a cane, face recognition and reading are the main necessary enabling capabilities.

The results and implications of fully functional visual prostheses are exciting. However, the challenges are grave. In order for a good quality image to be mapped in the retina a high number of micro-scale electrode arrays are needed. Also, the image quality is dependent on how much information can be sent over the wireless link. Also this high amount of information must be received and processed by the implant without much power dissipation which can damage the tissue. The size of the implant is also of great concern. Any implant would be preferred to be minimally invasive.

With this new technology, several scientists, including Karen Moxon at Drexel, John Chapin at SUNY, and Miguel Nicolelis at Duke University, started research on the design of a sophisticated visual prosthesis. Other scientists have disagreed with the focus of their research, arguing that the basic research and design of the densely populated microscopic wire was not sophisticated enough to proceed.

Auditory prosthetics

Cochlear implants (CIs), auditory brain stem implants (ABIs), and auditory midbrain implants (AMIs) are the three main categories for auditory prostheses. CI electrode arrays are implanted in the cochlea, ABI electrode arrays stimulate the cochlear nucleus complex in the lower brain stem, and AMIs stimulates auditory neurons in the inferior colliculus. Cochlear implants have been very successful among these three categories. Today the Advanced Bionics Corporation, the Cochlear Corporation and the Med-El Corporation are the major commercial providers of cochlea implants.

In contrast to traditional hearing aids that amplify sound and send it through the external ear, cochlear implants acquire and process the sound and convert it into electrical energy for subsequent delivery to the auditory nerve. The microphone of the CI system receives sound from the external environment and sends it to processor. The processor digitizes the sound and filters it into separate frequency bands that are sent to the appropriate tonotonic region in the cochlea that approximately corresponds to those frequencies.

In 1957, French researchers A. Djourno and C. Eyries, with the help of D. Kayser, provided the first detailed description of directly stimulation the auditory nerve in a human subject. The individuals described hearing chirping sounds during simulation. In 1972, the first portable cochlear implant system in an adult was implanted at the House Ear Clinic. The U.S. Food and Drug Administration (FDA) formally approved the marketing of the House-3M cochlear implant in November 1984.

Improved performance on cochlear implant not only depends on understanding the physical and biophysical limitations of implant stimulation but also on an understanding of the brain's pattern processing requirements. Modern signal processing represents the most important speech information while also providing the brain the pattern recognition information that it needs. Pattern recognition in the brain is more effective than algorithmic preprocessing at identifying important features in speech. A combination of engineering, signal processing, biophysics, and cognitive neuroscience was necessary to produce the right balance of technology to maximize the performance of auditory prosthesis.

Cochlear implants have been also used to allow acquiring of spoken language development in congenitally deaf children, with remarkable success in early implantations (before 2–4 years of life have been reached). There have been about 80,000 children implanted worldwide.

The concept of combining simultaneous electric-acoustic stimulation (EAS) for the purposes of better hearing was first described by C. von Ilberg and J. Kiefer, from the Universitätsklinik Frankfurt, Germany, in 1999. That same year the first EAS patient was implanted. Since the early 2000s FDA has been involved in a clinical trial of device termed the "Hybrid" by Cochlear Corporation. This trial is aimed at examining the usefulness of cochlea implantation in patients with residual low-frequency hearing. The "Hybrid" utilizes a shorter electrode than the standard cochlea implant, since the electrode is shorter it stimulates the basil region of the cochlea and hence the high-frequency tonotopic region. In theory these devices would benefit patients with significant low-frequency residual hearing who have lost perception in the speech frequency range and hence have decreased discrimination scores.

Prosthetics for pain relief

The SCS (Spinal Cord Stimulator) device has two main components: an electrode and a generator. The technical goal of SCS for neuropathic pain is to mask the area of a patient's pain with a stimulation induced tingling, known as "paresthesia", because this overlap is necessary (but not sufficient) to achieve pain relief. Paresthesia coverage depends upon which afferent nerves are stimulated. The most easily recruited by a dorsal midline electrode, close to the pial surface of spinal cord, are the large dorsal column afferents, which produce broad paresthesia covering segments caudally.

In ancient times the electrogenic fish was used as a shocker to subside pain. Healers had developed specific and detailed techniques to exploit the generative qualities of the fish to treat various types of pain, including headache. Because of the awkwardness of using a living shock generator, a fair level of skill was required to deliver the therapy to the target for the proper amount of time. (Including keeping the fish alive as long as possible) Electro analgesia was the first deliberate application of electricity. By the nineteenth century, most western physicians were offering their patients electrotherapy delivered by portable generator. In the mid-1960s, however, three things converged to ensure the future of electro stimulation.

1. Pacemaker technology, which had it start in 1950, became available.
2. Melzack and Wall published their gate control theory of pain, which proposed that the transmission of pain could be blocked by stimulation of large afferent fibers.
3. Pioneering physicians became interested in stimulating the nervous system to relieve patients from pain.

The design options for electrodes include their size, shape, arrangement, number, and assignment of contacts and how the electrode is implanted. The design option for the pulse generator include the power source, target anatomic placement location, current or voltage source, pulse rate, pulse width, and number of independent channels. Programming options are very numerous (a four-contact electrode offers 50 functional bipolar combinations). The current devices use computerized equipment to find the best options for use. This reprogramming option compensates for postural changes, electrode migration, changes in pain location, and suboptimal electrode placement.

Motor prosthetics

Devices which support the function of autonomous nervous system include the implant for bladder control. In the somatic nervous system attempts to aid conscious control of movement include Functional electrical stimulation and the lumbar anterior root stimulator.

Bladder control implants

Where a spinal cord lesion leads to paraplegia, patients have difficulty emptying their bladders and this can cause infection. From 1969 onwards Brindley developed the sacral anterior root stimulator, with successful human trials from the early 1980s onwards. This device is implanted over the sacral anterior root ganglia of the spinal cord; controlled by an external transmitter, it delivers intermittent stimulation which improves bladder emptying. It also assists in defecation and enables male patients to have a sustained full erection.

The related procedure of sacral nerve stimulation is for the control of incontinence in able-bodied patients.

Motor prosthetics for conscious control of movement

Researchers are currently investigating and building motor neuroprosthetics that will help restore movement and the ability to communicate with the outside world to persons with motor disabilities such as tetraplegia or amyotrophic lateral sclerosis. Research has found that the striatum plays a crucial role in motor sensory learning. This was demonstrated by an experiment in which lab rats' firing rates of the striatum was recorded at higher rates after performing a task consecutively.

To capture electrical signals from the brain, scientists have developed microelectrode arrays smaller than a square centimeter that can be implanted in the skull to record electrical activity, transducing recorded information through a thin cable. After decades of research in monkeys, neuroscientists have been able to decode neuronal signals into movements. Completing the translation, researchers have built interfaces that allow patients to move computer cursors, and they are beginning to build robotic limbs and exoskeletons that patients can control by thinking about movement.

The technology behind motor neuroprostheses is still in its infancy. Investigators and study participants continue to experiment with different ways of using the prostheses. Having a patient think about clenching a fist, for example, produces a different result than having him or her think about tapping a finger. The filters used in the prostheses are also being fine-tuned, and in the future, doctors hope to create an implant capable of transmitting signals from inside the skull wirelessly, as opposed to through a cable.

Prior to these advancements, Philip Kennedy (Emory and Georgia Tech) had an operable if somewhat primitive system which allowed an individual with paralysis to spell words by modulating their brain activity. Kennedy's device used two neurotrophic electrodes: the first was implanted in an intact motor cortical region (e.g. finger representation area) and was used to move a cursor among a group of letters. The second was implanted in a different motor region and was used to indicate the selection.

Developments continue in replacing lost arms with cybernetic replacements by using nerves normally connected to the pectoralis muscles. These arms allow a slightly limited range of motion, and reportedly are slated to feature sensors for detecting pressure and temperature.

Dr. Todd Kuiken at Northwestern University and Rehabilitation Institute of Chicago has developed a method called targeted reinnervation for an amputee to control motorized prosthetic devices and to regain sensory feedback.

In 2002 a Multielectrode array of 100 electrodes, which now forms the sensor part of a Braingate, was implanted directly into the median nerve fibers of scientist Kevin Warwick. The recorded signals were used to control a robot arm developed by Warwick's colleague, Peter Kyberd and was able to mimic the actions of Warwick's own arm. Additionally, a form of sensory feedback was provided via the implant by passing small electrical currents into the nerve. This caused a contraction of the first lumbrical muscle of the hand and it was this movement that was perceived.

In June 2014, Juliano Pinto, a paraplegic athlete, performed the ceremonial first kick at the 2014 FIFA World Cup using a powered exoskeleton with a brain interface. The exoskeleton was developed by the Walk Again Project at the laboratory of Miguel Nicolelis, funded by the government of Brazil. Nicolelis says that feedback from replacement limbs (for example, information about the pressure experienced by a prosthetic foot touching the ground) is necessary for balance. He has found that as long as people can see the limbs being controlled by a brain interface move at the same time as issuing the command to do so, with repeated use the brain will assimilate the externally powered limb and it will start to perceive it (in terms of position awareness and feedback) as part of the body.

Amputation techniques

The MIT Biomechatronics Group has designed a novel amputation paradigm that enables biological muscles and myoelectric prostheses to interface neurally with high reliability. This surgical paradigm, termed the agonist-antagonist myoneural interface (AMI), provides the user with the ability to sense and control their prosthetic limb as an extension of their own body, rather than using a prosthetic that merely resembles an appendage. In a normal agonist-antagonist muscle pair relationship (e.g. bicep-tricep), when the agonist muscle contracts, the antagonist muscle is stretched, and vice versa, providing one with the knowledge of the position of one's limb without even having to look at it. During a standard amputation, agonist-antagonist muscles (e.g. bicep-tricep) are isolated from each other, preventing the ability to have the dynamic contract-extend mechanism that generates sensory feedback. Therefore, current amputees have no way of feeling the physical environment their prosthetic limb encounters. Moreover, with the current amputation surgery which has been in place for over 200 years, 1/3 patients undergo revision surgeries due to pain in their stumps.

An AMI is composed of two muscles that originally shared an agonist-antagonist relationship. During the amputation surgery, these two muscles are mechanically linked together within the amputated stump. One AMI muscle pair can be created for each joint degree of freedom in a patient in order to establish control and sensation of multiple prosthetic joints. In preliminary testing of this new neural interface, patients with an AMI have demonstrated and reported greater control over the prosthesis. Additionally, more naturally reflexive behavior during stair walking was observed compared to subjects with a traditional amputation. An AMI can also be constructed through the combination of two devascularized muscle grafts. These muscle grafts (or flaps) are spare muscle that is denervated (detached from original nerves) and removed from one part of the body to be re-innervated by severed nerves found in the limb to be amputated. Through the use of regenerated muscle flaps, AMIs can be created for patients with muscle tissue that has experienced extreme atrophy or damage or for patients who are undergoing revision of an amputated limb for reasons such as neuroma pain, bone spurs, etc.

Obstacles

Mathematical modelling

Accurate characterization of the nonlinear input/output (I/O) parameters of the normally functioning tissue to be replaced is paramount to designing a prosthetic that mimics normal biologic synaptic signals. Mathematical modeling of these signals is a complex task "because of the nonlinear dynamics inherent in the cellular/molecular mechanisms comprising neurons and their synaptic connections". The output of nearly all brain neurons are dependent on which post-synaptic inputs are active and in what order the inputs are received. (spatial and temporal properties, respectively).

Once the I/O parameters are modeled mathematically, integrated circuits are designed to mimic the normal biologic signals. For the prosthetic to perform like normal tissue, it must process the input signals, a process known as transformation, in the same way as normal tissue.

Size

Implantable devices must be very small to be implanted directly in the brain, roughly the size of a quarter. One of the example of microimplantable electrode array is the Utah array.

Wireless controlling devices can be mounted outside of the skull and should be smaller than a pager.

Power consumption

Power consumption drives battery size. Optimization of the implanted circuits reduces power needs. Implanted devices currently need on-board power sources. Once the battery runs out, surgery is needed to replace the unit. Longer battery life correlates to fewer surgeries needed to replace batteries. One option that could be used to recharge implant batteries without surgery or wires is being used in powered toothbrushes. These devices make use of inductive coupling to recharge batteries. Another strategy is to convert electromagnetic energy into electrical energy, as in radio-frequency identification tags.

Biocompatibility

Cognitive prostheses are implanted directly in the brain, so biocompatibility is a very important obstacle to overcome. Materials used in the housing of the device, the electrode material (such as iridium oxide), and electrode insulation must be chosen for long term implantation. Subject to Standards: ISO 14708-3 2008-11-15, Implants for Surgery - Active implantable medical devices Part 3: Implantable neurostimulators.

Crossing the blood–brain barrier can introduce pathogens or other materials that may cause an immune response. The brain has its own immune system that acts differently from the immune system of the rest of the body.

Questions to answer: How does this affect material choice? Does the brain have unique phages that act differently and may affect materials thought to be biocompatible in other areas of the body?

Data transmission

Wireless Transmission is being developed to allow continuous recording of neuronal signals of individuals in their daily life. This allows physicians and clinicians to capture more data, ensuring that short term events like epileptic seizures can be recorded, allowing better treatment and characterization of neural disease.

A small, light weight device has been developed that allows constant recording of primate brain neurons at Stanford University. This technology also enables neuroscientists to study the brain outside of the controlled environment of a lab.

Methods of data transmission must be robust and secure. Neurosecurity is a new issue. Makers of cognitive implants must prevent unwanted downloading of information or thoughts from and uploading of detrimental data to the device that may interrupt function.

Correct implantation

Implantation of the device presents many problems. First, the correct presynaptic inputs must be wired to the correct postsynaptic inputs on the device. Secondly, the outputs from the device must be targeted correctly on the desired tissue. Thirdly, the brain must learn how to use the implant. Various studies in brain plasticity suggest that this may be possible through exercises designed with proper motivation.

Technologies involved

Local field potentials

Local field potentials (LFPs) are electrophysiological signals that are related to the sum of all dendritic synaptic activity within a volume of tissue. Recent studies suggest goals and expected value are high-level cognitive functions that can be used for neural cognitive prostheses. Also, Rice University scientists have discovered a new method to tune the light-induced vibrations of nanoparticles through slight alterations to the surface to which the particles are attached. According to the university, the discovery could lead to new applications of photonics from molecular sensing to wireless communications. They used ultrafast laser pulses to induce the atoms in gold nanodisks to vibrate.

Automated movable electrical probes

One hurdle to overcome is the long term implantation of electrodes. If the electrodes are moved by physical shock or the brain moves in relation to electrode position, the electrodes could be recording different nerves. Adjustment to electrodes is necessary to maintain an optimal signal. Individually adjusting multi electrode arrays is a very tedious and time consuming process. Development of automatically adjusting electrodes would mitigate this problem. Anderson's group is currently collaborating with Yu-Chong Tai's lab and the Burdick lab (all at Caltech) to make such a system that uses electrolysis-based actuators to independently adjust electrodes in a chronically implanted array of electrodes.

What people get wrong about herd immunity, explained by epidemiologists

There are two ways to reach herd immunity for Covid-19: the slow way, and the catastrophic way.

By Brian Resnick@B_resnickbrian@vox.com Updated Sep 28, 2020, 10:40am EDT

How will the Covid-19 pandemic end? And when?

These have been the biggest questions since the pandemic began earlier this year. The answer likely depends on one routinely misinterpreted concept in public health: herd immunity.

“Herd immunity is the only way we’re going to move to a post-pandemic world,” says Bill Hanage, an epidemiology researcher at Harvard. “The problem is, how do you get to it?”

Typically, the term herd immunity is thought of in the context of vaccination campaigns against contagious viruses like measles. The concept helps public health officials think through the math of how many people in a population need to be vaccinated to prevent outbreaks.

With Covid-19, since we don’t yet have a vaccine, the discussion has centered on herd immunity through natural infection, which comes with a terrible cost. Confusing matters, too, is the persistent and erroneous wishful thinking by some who say herd immunity has already been reached, or will be reached sooner than scientists are saying.

For instance, at a recent Senate hearing, Sen. Rand Paul (R-KY) claimed that New York City has its outbreak under control thanks to herd immunity and the fact that around 22 percent of the city’s residents had been infected.

But Dr. Anthony Fauci of the National Institutes of Health, who was a panelist at the hearing, immediately spoke up to correct the senator: “If you believe 22 percent is herd immunity, I believe you’re alone in that.”

Related

“It isn’t a question of politics”: Fauci on calling out Sen. Rand Paul’s misinformation

Hypothetically, yes, there are situations under which herd immunity to Covid-19 could be achieved. Manaus, Brazil, an Amazonian city of around 2 million people, experienced one of the most severe Covid-19 outbreaks in the world. At the peak in the spring and early summer, the city’s hospitals were completely full, the New York Times reported.

During this period, there were four times as many deaths as normal for that point in the year. But then, over the summer, the outbreak sharply died down. Researchers now estimate between 44 percent and 66 percent of the city’s population was infected with the virus, which means it’s possible herd immunity has been achieved there. (This research has yet to be peer-reviewed.)

But that’s much higher than 22 percent, and the cost of this herd immunity was immense: Between 1 in 500 and 1 in 800 residents died there, the researchers estimate.

Many more were hospitalized, and still more may suffer long-term consequences of the infection. Similarly, the oft-cited example of Sweden, which has pursued a laxer social distancing strategy than its European peers (partially with the goal of building up herd immunity in younger people, while protecting older residents and trying to keep hospitals from exceeding capacity), has paid a price, too: a much higher death rate than fellow Scandinavian countries.

We’re several months into this pandemic, and herd immunity is still widely misunderstood and being continually misused for partisan goals of discrediting science and scientists. The biggest misconception is that achieving herd immunity through natural infection is a reasonable pandemic response strategy. It’s not. Let’s explain.

Herd immunity, explained, simply

There’s a simple explanation of herd immunity.

After a certain proportion of a population has become immune to a virus, an outbreak will stop growing exponentially. There may continue to be new cases, but each new case will be less likely to start a big chain of infections.

In this simple view, the herd immunity threshold — that specific proportion of the population with some immunity — is derived from a value called the R0 (r-naught). This is the figure that quantifies the average transmissibility of a disease. If the R0 is 2, that means that, on average, each case will lead to fewer than two new cases.

So the herd immunity threshold for a disease of this contagiousness is 50 percent. When half the population becomes immune, then, the outbreak may start to decline because the virus will not be able to spread as easily. For Covid-19, the exact figure for the threshold depends on whom you ask. Based on the simple math, “the expectation for the natural herd immunity level for Covid would be 60 to 75 percent,” Shweta Bansal, a Georgetown University epidemiologist, says. Though the figure could be a bit lower, perhaps 40 percent, in some places.

Regardless of the exact figure, as a country, the US is nowhere near reaching this threshold. In New York City, which experienced the worst coronavirus outbreak in the US, around 20 percent of residents got infected and 23,000-plus people died. Overall, a new Lancet study — which drew its data from a sample of dialysis patients — suggests that fewer than 10 percent of people nationwide have been exposed to the virus. That means we have a long, sick, and deadly way to go if the US is going to reach herd immunity through natural infection.

So far, there have been more than 200,000 deaths in the United States, with relatively few infections. There’s so much more potential for death if the virus spreads to true herd immunity levels. “The cost of herd immunity [through natural infection] is extraordinarily high,” Hanage says.

The herd immunity threshold for Covid-19 could be lower, or higher, than 60 percent. It depends on the makeup of a community, and its social dynamics.

So that’s the simple math of herd immunity — it’s a fraction derived from the R0 of the virus. Easy, right? In reality, how herd immunity through natural infection plays out in the real world is much messier, and very hard to precisely predict.

For one, this simple mathematical view of herd immunity assumes that risk of catching the disease in a population is evenly distributed. But we know that isn’t the case with Covid-19.

Risk of catching the virus varies greatly and in a number of dimensions. Here, physician and virology expert Muge Cevik breaks down the dimensions of risk:

As we’ve seen, some people are more at risk of infection and severe illness or death because of their job, the environments they live and work in, the makeup of their immune system, socioeconomic factors like poverty, or their behavior: Some people may be willfully disregarding social distancing and mask-wearing mandates.

Knowing that the population doesn’t evenly share risk means the threshold for herd immunity can change based on who gets infected. Let’s say all the people most at risk of both catching and spreading the virus all get infected first. Then “the immunity within that group will have a particularly outsize benefit,” Hanage says. “Because they are the core group driving infection.”

So the overall threshold for herd immunity will be lower. How much lower?

Some hypothetical estimates put it as low as 20 percent, but “I think that is a stretch,” Bansal says. “Is [the herd immunity threshold] lower than 60 percent? Sure, that’s entirely possible. But I again, I think I don’t want any place on the planet to get to anything even close to that, right, in terms of infection rates.”

Hanage underscores a gross inequality here: Herd immunity achieved through natural infection would come at an undue cost to some of the most vulnerable, marginalized groups in the country.

“Because of the fact that some groups are more at risk of becoming infected than others — and they are predominantly people from racial [and] ethnic minorities and predominantly poor people with less good housing — we are effectively forcing those people to have a higher risk of infection and bear the brunt of the pandemic,” Hanage says.

The herd immunity threshold can be lower than estimated. But hypothetically, the threshold could be higher as well. It’s also the case that the herd immunity threshold can change over time. Remember the simple math of how herd immunity calculated: The threshold is dependent on the contagiousness of the virus.

Well, the contagiousness of the virus isn’t a fixed biological constant. It’s the result of the biology of the virus interacting with human biology, with our environments, with our society. As seasons change, as our behavior changes, so can the transmissibility of the virus. The herd immunity threshold is not one fixed target.

Herd immunity doesn’t end the pandemic. It just slows it down.

Once you hit the herd immunity threshold, it doesn’t mean the pandemic is over. After the threshold is reached, “all it means is that on average, each infection causes less than one ongoing infection,” Hanage says. “That’s of limited use if you’ve already got a million people infected.” If each infection causes, on average, 0.8 new infections, the epidemic will slow. But 0.8 isn’t zero. If a million people are infected at the time herd immunity is hit, per Hanage’s example, those already infected people may infect 800,000 more.

There are a lot of other unknowns here, too. One is the type of immunity conferred by natural infection. “Immunity” is a catchall term that means many different things. It could mean true protection from getting infected with the virus a second time. Or it could mean reinfections are possible but less severe. You could, potentially, get infected a second time, never feel sick at all (thanks to a quick immune response), and still pass on the virus to another person. “If immunity just reduces disease ... then [the] concept loses meaning,” Sarah Cobey, a computational biologist at the University of Chicago, writes in an email, noting, though, that this scenario is “unlikely.”

Overall, we don’t know if herd immunity through natural infection would look the same as herd immunity achieved through a vaccination campaign. “We don’t know yet if those two things will be different,” Christine Tedijanto, an epidemiology researcher at Harvard, says.

Even New York City could see another big wave

Right now, New York City appears to have its epidemic mostly under control, with fewer than 200 new cases a day, down from a springtime high of more than 5,000 cases per day. But the progress is precarious, with city health officials growing concerned about increasing clusters of cases in several of the city’s neighborhoods. Mayor Bill de Blasio said the city needs to take “urgent action” to prevent these clusters from growing.

It’s possible there are pockets of herd immunity in some New York communities, and, overall, it’s estimated around 20 percent of the city’s residents contracted the virus. Despite what Sen. Paul might think, New York has achieved some control through measures like social distancing and mask-wearing.

“As soon as they lift their foot off the brake, they will see that outbreak come back,” Bansal says. The reason New York has the epidemic under control is not because it’s achieved herd immunity; it’s because it's gotten its act together.

But even if there’s some degree of protection in New York from the natural infections that have occurred there, that protection will only last while mitigation measures are in place.

Another way to think about it: Through control measures, New York City has successfully, and artificially, reduced the transmissibility of the virus. That temporarily lowers the bar for the herd immunity threshold. But the city can’t resume life as it went on before the pandemic struck. That would increase the transmissibility of the virus, and the epidemic would grow there until reaching a higher herd immunity threshold.

Also, in New York, it’s important to remember that the level of immunity could vary widely from one community to the next. “Even if one borough has reached a herd immunity threshold, the boroughs around it may not have,” Tedijanto says.

Why you can’t infect the young to protect the old

Let’s say herd immunity is achieved through millions of younger people getting sick. White House adviser Scott Atlas (who is a neuroradiologist, not an epidemiologist) has suggested this is a good thing to do. “When younger, healthier people get infected, that’s a good thing,” he said in a July interview with a San Diego local news station. “The goal is not to eliminate all cases. That’s not rational, not necessary if we just protect the people who are going to have serious complications.”

Let’s be clear, it’s not a “good thing” when young people get sick. For one, some of these young people may die, more may get severely ill, and a not-yet-understood proportion of them could suffer long-term consequences. Remember: The more people infected, the more chances for rare, horrible things to happen.

These younger people, now immune, could, in theory, protect older populations more at risk of dying from Covid-19. But in building up herd immunity in this way, we’ve also built up powder kegs of vulnerability among the older people, which can be set off in the future.

“I think it’s impossible to think that you can have infections only among younger people, and not let them spread to other groups with populations that might be more vulnerable,“ Tedijanto says. People just don’t separately themselves so neatly into risk groups like that.

“We can try and insulate” older people, Hanage says. “We can do a very good job of insulating them. But the fact is, the larger the amount of infection outside them, the higher the chance that something’s going to get into them.”

Overall, here’s the biggest problem with thinking about herd immunity through natural infection: It’s impossible to predict which route it is going to go. “We don’t understand and measure our world in very deep ways yet,” Bansal says. We can’t predict the movements and behaviors, the risk factors, of millions of people, and how they change over time. Allowing herd immunity to develop through natural infection means letting the virus rip a hard-to-predict course through the population.

Herd immunity isn’t a dirty word. When a vaccine comes, it will be essential for scientists to devise a strategy to most effectively inoculate the country and end the pandemic. The price of achieving herd immunity through a vaccine campaign is the price of the vaccine, and the price of our patience waiting for it.