Scientific and Medical Publishing: Role and Definition of Authors

What do the editors of medical journals talk about when they get together?

So far today, it’s been a fascinating but rather grim mixture of research that can’t be replicated, dodgy authorship, plagiarism and duplicate papers, and the general rottenness of citations as a measure of scientific impact.

We’re getting to listen and join in the editors’ discussion  in Chicago in the year 2013 (7th International Congress on Peer Review and Biomedical Publication). They assemble once every four years to chew over academic research on scientific publishing and debate ideas. This tradition was started by The Journal of American Medical Association, JAMA in Chicago in 1989. The name of the international congress still goes by its original pre-eminent concern, “peer review and biomedical publication.” But the academic basis for peer review is a small part of what’s discussed these days.

The style hasn’t changed in all these years, and that’s a good thing. As JAMA contributing deputy editor Drummond Rennie  said, most medical conferences go on and on, “clanking rustily forward like a Viking funeral.” Multiple concurrent sessions render a shared ongoing discussion impossible.

The congress hurtled off to an energetic start with John Ioannidis, epidemiologist and agent provocateur author of “Why most published research findings are false.” He pointed to the very low rate of successful replication of genome-wide association studies (not much over 1%) as an example of very deep-seated problems in discovery science.

Half or more of replication studies are done by the authors of the original research: “It’s just the same authors trying to promote their own work.” Industry, he says, is becoming more concerned with replicability of research than most scientists are. Ioannidis cited a venture capital firm that now hires contract research organizations to validate scientific research before committing serious funds to a project.

Why is there so much un-reproducible research? Ioannidis points to the many sources of bias in research. Chavalarias and he trawled through more than 17 million articles in PubMed and found discussion of 235 different kinds of bias. There is so much bias, he said, that it makes one of his dreams – an encyclopedia of bias – a supremely daunting task.

Authorship Issues & Postdocs - No it is my wifes turn to be first author on your paper.

What would help?

Ioannidis said we need to go back to considering what science is about: “If it is not just about having an interesting life or publishing papers, if it is about getting closer to the truth, then validation practices have to be at the core of what we do.” He suggested three ways forward:

  1. we have to get used to small genuine effects and not expect (and fall for) excessive claims.
  2. Secondly, we need to have – and use – research reporting standards.
  3. The third major strategy he advocates is registering research: protocols through to datasets.

Isuru Ranasinghe, in a team from Yale, looked at un-cited and poorly cited research in cardiovascular research. The proportion isn’t changing over time, but the overall quantity is rising rather dramatically as the biomedical literature grows: “1 in 4 journals have more than 90% of their content going un-cited or poorly cited five years down the track.” Altogether, about half of all articles don’t have an influence – if you judge it by citation.

Earlier, though, there was a lot of agreement from the group on the general lousiness of citation as a measure and influence on research. Tobias Opthof, presenting his work on journals pushing additional citation of their own papers, called citation impact factors “rotten” and “stupid”. Elizabeth Wager pulled no punches at the start of the day, reporting on analyses of overly prolific authors: surely research has to be about doing research, not just publishing a lot of articles. Someone who publishes too many papers, she argued, could be of even more concern than someone who does research, but publishes little. Incentives and expectations of authorship really no longer serve us well – if they ever did. [Bad research rising: The 7th Olympiad of research on biomedical publication]

One of the highlights of graduate school is publishing your very first papers in peer-reviewed journals. But what this novice scientist should not be fretting over is which colleagues should be included as authors and whether they are breaking any norms. The two things that should be avoided are including as authors, those that did not substantially contribute to the work, and excluding those that deserve authorship. There have been controversial instances where breaking these authorship rules caused uncomfortable situations. None of us would want someone writing a letter to a journal arguing that they deserved authorship. Nor is it comfortable to see someone squirming out of authorship, arguing they had minimal involvement when an accusation of fraud has been levelled against a paper. How to determine who should be an author can be difficult.

The cartoon above highlights the complexity and arbitrariness of authorship –and the perception that there are many instances of less than meritorious inclusion.

Journals do have their own guidelines, and many now require statements about contributions, but even these can be vague, still making it difficult to assess how much individuals actually contributed. We usually reiterate the criteria from Weltzin et al. (2006)[Weltzin, J. F., Belote, R. T., Williams, L. T., Keller, J. K. & Engel, E. C. (2006) Authorship in ecology: attribution, accountability, and responsibility. Frontiers in Ecology and the Environment, 4, 435-441]. There are four criteria to evaluate contribution:

  1. Origination of the idea for the study. This would include the motivation for the study, developing the hypotheses and coming up with a plan to test hypotheses.
  2. Running the experiment or data collection. This is where the blood, sweat and tears come in.
  3. Analysing the data. Basically moving from a database to results, including deciding on the best analyses, programming (or using software) and dealing with inevitable complexities, issues and problems.
  4. Writing the paper. Putting everything together can sometimes be the most difficult and external motivation can be important.

Basic requirements for authorship are that one of these steps was not possible without a key person, or else there was a person who significantly contributed to more than one of these. Such requirements mean that undergraduates assisting with data collection do not meet the threshold for authorship. Obviously these are idealized and different types of studies (e.g., theory or methodological papers) do not necessarily have all these activities. Regardless, authors must have contributed in a meaningful way to the production of this research and should be able to defend it. All authors need to sign off on the final product. [Navigating the complexities of authorship: Part 1 –inclusion]

While this system is idealized, there are still complexities making authorship decisions difficult or uncomfortable.

I recently came across an article “AUTHORSHIP: AN EVOLVING CONCEPT”.

It deals with the role and definition of authorship and the need to differentiate between an “author” and a “contributor”.

As most of us often write an article or a study to be published in a journal or a magazine, I thought it would be necessary to share it with everyone, as simply providing a link would have let it gone unnoticed.

Authorship confers credit and has important academic, social, and financial implications. Authorship also implies responsibility and accountability for published work.

Manuscript Rejection - where are those editors these days.

Authorship: An Evolving Concept

By Steph Fairbairn, Leanne Kelly, Selina Mahar, and Reinier Prosée, editorial coordinators, Health Learning, Research & Practice, Wolters Kluwer

The role and definition of authorship in scientific and medical publishing has become increasingly complicated in recent years.

In most other forms of publishing – social sciences, humanities, legal – we assume that three, perhaps four, authors collaborated in the writing of the work. However, the nature of scientific research and reporting means that “authorship” no longer fits into a neat category.

To elaborate, a researcher who didn’t write the text of a paper can still be considered an author if her or she contributed substantially to the conception of the work, or the analysis of the data. Access to the Internet has made sharing information and collaborating on projects far simpler, and many authors can now work closely with colleagues in different countries.

With such a proliferation of collaboration and co-authorship in academic writing, it becomes harder to differentiate between a “contributor” and an “author.” Moreover, the pressures of funding applications, securing tenure at an academic institution, and the requirement to meet publication quotas all play their part in pushing contributors to demand a co-authorship accreditation.

Plagiarism. With thanks to google images.

Plagiarism is the copying or paraphrasing of other people’s work or ideas into your own work without full acknowledgement.

ICMJE Guidelines

The International Committee of Medical Journal Editors (ICMJE) formulated a set of guidelines to define authorship. [The New ICMJE Recommendations (August 2013). The International Committee of Medical Journal Editors.]

One of the most important changes in the document is the addition of a fourth criterion for authorship to emphasize each author’s responsibility to stand by the integrity of the entire work.

Authorship requires:

  • Substantial contributions to: the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; AND
  • Drafting the work or revising it critically for important intellectual content; AND
  • Final approval of the version to be published; AND
  • Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. [Defining the Role of Authors and Contributors. The International Committee of Medical Journal Editors.]

Authorship involves not only credit for the work but also accountability. The addition of a fourth criterion was motivated by situations in which individual authors have responded to inquiries regarding scientific misconduct involving some aspect of the study or paper by denying responsibility (“I didn’t participate in that part of the study or in writing that part of the paper; ask someone else”). Each author of a paper needs to understand the full scope of the work, know which co-authors are responsible for specific contributions, and have confidence in co-authors’ ability and integrity. When questions arise regarding any aspect of a study or paper, the onus is on all authors to investigate and ensure resolution of the issue.

By accepting authorship of a paper, an author accepts that any problem related to that paper is, by definition, his or her problem. Given the specialized and myriad tasks frequently involved in research, most authors cannot participate directly in every aspect of the work. Still, ICMJE holds that each author remains accountable for the work as a whole by knowing who did what, by refraining from collaborations with co-authors whose integrity or quality of work raises concerns, and by helping to resolve questions or concerns if they arise. For example, a clinician who merits authorship in part through design of a study and care of its participating patients should have full confidence in the work of co-authors with expertise in biostatistics, and must agree as a condition of authorship to ensure resolution of questions regarding the analysis should they arise. This new criterion better balances credit with responsibility, and establishes the expectation that editors may engage all authors in helping to determine the integrity of the work.

The authorship criteria are not intended for use as a means to disqualify colleagues from authorship who otherwise meet authorship criteria by denying them the opportunity to meet criterion #s 2 or 3. Therefore all individuals who meet the first criterion should have the opportunity to participate in the review, drafting, and final approval of the manuscript. As always the decision about who should be an author on a given article is the responsibility of the authors and not the editors of the journal to which the work has been submitted.

Non-Author Contributors

Contributors who meet fewer than all 4 of the above criteria for authorship should not be listed as authors, but they should be acknowledged. Examples of activities that alone (without other contributions) do not qualify a contributor for authorship are

  • acquisition of funding; general supervision of a research group or general administrative support;
  • and writing assistance, technical editing, language editing, and proofreading.

Those whose contributions do not justify authorship may be acknowledged individually or together as a group under a single heading (e.g. “Clinical Investigators” or “Participating Investigators”), and their contributions should be specified (e.g., “served as scientific advisors,” “critically reviewed the study proposal,” “collected data,” “provided and cared for study patients”, “participated in writing or technical editing of the manuscript”).

Coauthor List - You should spend the next week typing down names of all co-authors on your paper.Some researchers have argued that these guidelines are unfairly strict, but they were created to safeguard the idea of authorship to signify scientific integrity. Readers do not want a meaningless list of names – they want to know who is chiefly responsible.[Scott T. Changing authorship system might be counterproductive. BMJ 1997; p. 744]

 In this way, adhering to the ICMJE definition ensures that only those who are “chiefly responsible” are recognized and held accountable. Some authors, however, take issue with the ICMJE guidelines not just because they require authors to be involved in every stage of the manuscript’s production, but because they wish to acknowledge the important contribution of their colleagues. In their editorial “The Men Who Stare at Science,” Goetze and Reinfeld argue that senior scientists should “grab the pen (keyboard) more often” as writing “is essential to ones results and to harbour new ideas.” [Goetze, Jens P.; Rehfeld, Jens F. The men who stare at science. Cardiovascular Endocrinology 2015; p. Published ahead of print.]

Postdoc Workload - Just work till midnight you need to relax too.

Historical overview

Taking a broad look at the history of authorship, even going back to the classical period, you can see how ideas of authorship have only recently become intertwined with ideas of ownership and uniqueness (see The origins of our current understanding of authorship). In Laws, Plato argues that we should “eliminate everything we mean by the word ownership,” which includes intellectual property.Plato rejected the notion of uniqueness and believed that new knowledge is something that we relearn. [Hamilton E, and Cairns H (Translators). Plato. The Collected Dialogues: Including the Letters.   Princeton, New Jersey: Princeton University Press; 1961.]

Not every Classical author shared this belief, however, and some took more credit for their work. Herodotus, for example, starts his famous Histories by mentioning that “Herodotus, from Halicarnassus, here displays his enquiries.” [Holland T (Translator). Herodotus: The Histories. London: Penguin Classics; 2013.]

Herodotus is keen to outline clear rules regarding the correct citation of sources, but in the Classical period plagiarism was common as authors and orators shared the same sources and borrowed from one another.

[Anderson J. Plagiarism, Copyright Violation and Other Thefts of Intellectual Property: An Annotated Bibliography with a Lengthy Introduction. Jefferson, North Carolina and London: McFarland & Company, Inc., Publishers; 1998.]

Current Understanding of Authorship

During the Renaissance, the idea of an author’s ownership of a text came into being, particularly with the Statute of Anne (1710), which conferred ownership to authors rather than publishers; it is no surprise that this development coincided with the rise of the printing press. This early form of copyright did not apply to content, [Velagic Z, Hasenay D. Understanding textual authorship in the digital environment: lessons from historical perspectives. Proceedings of the Eighth International Conference on Conceptions of Library and Information Science, Copenhagen, Denmark; 2013]

but it was an important step toward the idea of intellectual property developed in the Romantic period. The Romantic Movement emphasized the importance of the individual, which led to intellectual and creative copyright laws being consolidated during the 19th century.

[Velagic Z, Hasenay D. Understanding textual authorship in the digital environment: lessons from historical perspectives. Proceedings of the Eighth International Conference on Conceptions of Library and Information Science, Copenhagen, Denmark; 2013]

It wasn’t until postmodernist critiques of literary theory, in the middle of the 20th century, that ideas of individualism were challenged. In particular, Roland Barthes rejected the Romantic idea of individualism and ownership. In Barthes’ now infamous essay “The Death of the Author” (1967), he argued that authorial intention should be separated from the text. Barthes decentred the author, going against the traditional theory that an author’s history and experience could be used to enrich our understanding of his or her work.

Current author trends

The debate over authorship and contributorship was reignited in March 2015, when G3: Genes|Genomics|Genetics published a paper on the genomics of the fruit fly with over 1,000 listed authors.

[Leung, W. et al. Drosophila Muller F Elements Maintain a Distinct Set of Genomic Properties Over 40 Million Years of Evolution. G3: Genes|Genomics|Genetics. 2015.]

According to Barthes’ theory, if the “author” is simply representative of his or her institution, or academic background, why not include all those directly involved in its creation? 

[Woolston, C. Fruit-fly paper has 1,000 authors. Nature. 2015.]

Each undergraduate student contributed to the analysis of data, which is one of the major tenants of authorship according to the ICMJE. If we understand the author as the progenitor of this article, then logic follows that each person listed as a co-author contributed to the authorship of the paper, however small. To take this one step further, the identity of each co-author eventually becomes subsumed into the first author when a paper is cited as W. Leung et al, and the number of contributors is incidental because of how papers are traditionally cited with the use of et al.”

Throughout history, writing has commonly been regarded as an individual act. People like to associate one paper, or idea, with one name. Examples of this include Edward Jenner and the production of the first vaccines, Alexander Fleming and the discovery of penicillin, and Marie Curie and the development of radiotherapy. In recent years, however, as scientific papers are increasingly authored through collaborative efforts rather than individuals, this has opened up the dilemma of first authorship. In 1996 it was suggested that the tradition of citing authors should be restructured to parallel film credits and create a hierarchy of authorship, contributors, and acknowledgements.

[Godlee F; Definition of “authorship” may be changed; BMJ. 1996 Jun 15;312(7045):1501-2.]

This concept would not redefine authorship but instead recognize important contributions in another way. While this idea is attractive, it doesn’t solve the problem of who to list as an author and who to list as a contributor.



Let’s Build a Culture of Integrity Instead!


One potential solution was recently proposed by BioMed Central to implement

“Author Contributorship Badges”

as a method of showing the exact contribution each author made to a paper. [BioMed Central first publisher to implement Author Contributorship Badges, a new system which improves how publishers credit scientists. BioMed Central. 2015]

BioMed Central chose to roll this scheme out in their open-access, open-data journal, GigaScience. All papers published from October 1, 2015, will include the badge system (see First paper published by BioMed Science with Author Contributorship Badges). While authors are still listed in the traditional format, a link to the “Open Badges” appears on the website, and ten potential roles in the creation of an article are represented by ten badges, such as “Data Curation,” “Methodology,” and “Writing Review.”

ScreenHunter_67 Oct. 09 08.58ScreenHunter_66 Oct. 09 08.56ScreenHunter_64 Oct. 09 08.55ScreenHunter_63 Oct. 09 08.54

BioMed Central Implements Author Contributorship Badges


Each badge has a list of authors who contributed to that specific role, and an author can be listed under more than one role. Amye Kenall, associate publisher at BioMed Central, states: “Author Contributorship Badges enable people and organisations to capture the types of skills, knowledge and behaviours that we value, but often find difficult to recognise with traditional credentials.”

The badge system embraces the ICMJE definition of authorship in a refreshing format. Each point in the ICMJE definition has at least one badge. Should it prove successful, the badge system could be a significant turning point in how authors and publishers define authorship.

Badges Biomed Central.png

GWATCH: a web platform for automated gene association discovery analysis 

Svitin, A., Malov, S., Cherkasov, N., Geerts, P., Rotkevich, M., Dobrynin, P., & … O’Brien, S. J. (2014). GWATCH: a web platform for automated gene association discovery analysis.Gigascience, 318. doi:10.1186/2047-217X-3-18

The future of authorship

One of the most significant changes in the publishing industry has been the shift toward digital media and the steady decline of print. Authors are no longer being asked to write a finite article for a journal. For example, when an author contributes an article to a journal, the article will be published in the print and digital versions, shared on social media, and potentially used in promotional material.

This notion of multiple destinations is even more evident when considering blogs. When an author writes a blog, he or she is writing with the knowledge that the work can be shared, critiqued, and linked in numerous ways, making it not just a blog post or a text but part of a huge textual network.

A text is no longer a finished article;

it is an

“ongoing conversation,”

a fluid movement with a number of versions and stages.

[Fitzpatrick, K; The Digital Future of Authorship: Rethinking Originality; Culture Machine; 2011, Vol 12,]

It lives under the assumption that any text, online-only or complimentary to a print component, should constantly be changing. When putting a text on the Internet, particularly in blog form, the text is immediately visible for public consumption and critique. A blog creates a forum for all views, and the result combines numerous views on one topic, while adding commentary to create a new text.

The fluid nature of blogs and other online formats has introduced the idea of “versioning.”

This is traditionally defined as “the creation and management of multiple releases of a product, all of which have the same general function but are improved, upgraded, or customized.”

[Versioning Definition. 2007.

The same, or an alternate, author takes an article and makes changes. He or she adds to it, improving it and creating a timelier and more informative piece; more authors can also be added to the text.

Versioning allows readers to see a scientific process not just through the words of a text, but through the progression of the text itself. With this change of process, the act of writing becomes less about the act itself, or the completion of a piece of work, and more about development and discovery. This, in turn, could mean that authors will no longer be defined by specific works, but by one work as a whole.

However, the prospect of a more fluid style of writing and authorship will inevitably lead to a number of potential problems, namely plagiarism. The traditional notion of plagiarism is that all those involved in the writing of a paper are named as authors, giving due credit for anything they may have borrowed or used in their text. With a more fluid, ever-evolving text, plagiarism (whether intentional or unintentional) is inevitable and perhaps unavoidable. The idea of a constantly reworked text also raises a number of questions about the validity of the work and the contributions of different authors –

are the authors involved sufficiently in the work to be considered as such?

Could they be considered as “curators” instead?

Is the work more about quantity than quality?

Who is chosen as the “first author” after so many changes to a paper?

How will original authors feel about their works being up for adaptation and public consumption?

Most importantly, with articles constantly changing, how will publishers and readers assure their legitimacy?

As we move further into the digital age, these questions require discussion in order to redefine the concept of authorship. In many ways, it seems as though we are trying to embrace the new freedoms that digital media allows while maintaining strong traditions in print and also trying to identify the most modern definition of authorship. Although the “Author Contributorship Badges” offer an appealing solution it is, after-all, online-only. What is certain is the need for the academic and publishing communities to continue their discussion on the definition of authorship, ensuring clarity and flexibility in an increasingly digital age. In the meantime, the ICMJE guidelines provide a definition of authorship that guarantees recognition, both by authors and for authors. In time, they will surely be modified to reflect digital trends, but for now, they clearly delineate what it means to be an author.

Reference: AUTHORSHIP: AN EVOLVING CONCEPT                             Authors
Steph Fairbairn, Leanne Kelly, Selina Mahar, and Reinier Prosée
Editorial coordinators, Health Learning, Research & Practice | Wolters Kluwer


Microglia – Trying to Set a New Paradigm in the Realm of Brain’s Development, Homeostasis & Diseases

Microglia Cells Accelerate Damage from Retinitis Pigmentosa, Other Blinding Eye Diseases; Finding May Suggest Entirely New Therapeutic Strategies; Targeting Microglia May Complement Gene Therapy for RP

The traditional role of microglia has been in brain infection and disease, phagocytosing debris and secreting factors to modify disease progression.

Recent evidence extends their role to healthy brain homoeostasis, including the regulation of cell death, synapse elimination, neurogenesis and neuronal surveillance. These actions contribute to the maturation and plasticity of neural circuits that ultimately shape behaviour.

Gardeners know that some trees require regular pruning: some of their branches have to be cut so that others can grow stronger.

The same is true of the developing brain: cells called microglia prune the connections between neurones, shaping how the brain is wired.[]

Electron micrograph showing the interaction of microglia (immunolabeled with and antibody to Iba1) and synaptic elements. Blue: axon terminal; Purple: dendrite and dendritic spine; Pink: microglia; Green: astrocyte. Scale bar: 250nm.

Microglia, the immune cells of the brain, have long been the underdogs of the glia world, passed over for other, flashier cousins, such as astrocytes. Although microglia are best known for being the brain’s primary defenders, scientists now realise that they play a role in the developing brain and may also be implicated in developmental and neurodegenerative disorders.

The change in attitude is clear, as evidenced by the buzz around this topic at this year’s Society for Neuroscience (SfN) conference, which took place from October 17 to 21 in Chicago (2015), where scientists discussed their role in both health and disease.

Activated in the diseased brain, microglia finds injured neurones and strip away the synapses, the connections between them. These cells make up around 10 percent of all the cells in the brain and appear during early development.

For decades scientists focussed on them as immune cells and thought that they were quiet and passive in the absence of an outside invader. That all changed in 2005 when experimenters found that microglia were actually the fastest-moving structures in a healthy adult brain. Later discoveries revealed that their branches were reaching out to surrounding neurones and contacting synapses. These findings suggested that these cellular scavengers were involved in functions beyond disease.

Microglial dynamics 

(In vivo imaging of microglial dynamics in Cx3CR1-GFP mice. Images were taken 5 minutes apart. Notice that dynamic microglial processes constantly explore the brain environment.)


Types of Synapses Image source


The Brain’s Sculptors

The discovery that microglia were active in the healthy brain jump-started the exploration into their underlying mechanisms:

Why do these cells hang around synapses?

And what are they doing?

For reasons scientists don’t yet understand, the brain begins with more synapses than it needs. “As the brain is making it’s [connections], it’s also eliminating them,” says Cornelius Gross, a neuroscientist at the European Molecular Biology Laboratory. Microglia a critical to this process, called pruning: they gobble up synapses, thus helping to sculpt the brain by eliminating unwanted connections.

But how do microglia know which synapses to get rid of and which to leave alone?

New evidence suggests that a protective tag that keeps healthy cells from being eaten by the body’s immune system may also shield against microglial activity in the brain. Emily Lehrman, a doctoral candidate in neuroscientist Beth Stevens’s laboratory at Boston’s Children’s Hospital, presented these unpublished findings at this year’s SfN (Society for Neuroscience (SfN) conference).

“The [protective tag]’s receptor is highly expressed in microglia during peak pruning,” Lehrman says. Without an abundance of this receptor, the tag is unable to protect the cells, leading to excess engulfment by microglia and overpruning of neuronal connections.

 But pruning is not always a bad thing. Other molecules work to ensure that microglia removes weak connections, which can be detrimental to brain function.

Cornelius Gross, a neuroscientist at the European Molecular Biology Laboratory, and his research group have been investigating the activity of fractalkine, a key molecule in neuron-microglia signalling whose receptors are found exclusively on microglia. “Microglia mature in a way that matches synaptogenesis, which sets up the hypothesis that neurones are calling out to microglia during this period,” Gross says.

His lab found that removing the receptor for fractalkine created an overabundance of weak synaptic contacts caused by deficient synaptic pruning during development in the hippocampus, a brain area involved in learning and memory. These pruning problems led to decreased functional connectivity in the brain, impaired social interactions and increased repetitive behaviour—all telltale signs of autism. Published last year in Nature Neuroscience, this work was also presented at the conference.

When Pruning Goes Awry

Studies have also found evidence for increased microglial activation in individuals with schizophrenia and autism; however, whether increased microglial activity is a cause or effect of these diseases is unclear. “We still need to understand whether pruning defects are contributing to these developmental disorders,” Stevens says.

Some findings are emerging from studies on Rett syndrome, a rare form of autism that affects only girls. Dorothy Schafer, now at the University of Massachusetts Medical School, studied microglia’s role in Rett syndrome while she was a postdoctoral researcher in Stevens’s lab. Using mice with mutations in MECP2, the predominant cause of the disease, she found that while microglia were not engulfing synapses during early development, the phagocytic capacity (or the gobbling ability) of these cells increased during the late stages of the disease. These unpublished results suggest that microglia were responding secondarily to a sick environment and partially resolve a debate going on about what microglia do in Rett syndrome—in recent years some studies have shown that microglia can arrest the pathology of disease, whereas others have indicated that they cannot. “Microglia are doing something, but in our research, it seems to be a secondary effect,” Shafer says. “What’s going on is still a huge mystery.”

Activated microglial cells (red) among a GFP-expressing neurone and astrocyte (green) in a rat hippocampal tissue slice.

Return of the Pruning Shears

As the resident immune cells, microglia act as sentinels, sensing and removing disturbances in the brain. When the brain is exposed to injury or disease, microglia surrounds the damaged areas and eat up the remains of dying cells. In Alzheimer’s disease, for example, microglia are often found near the sites of beta-amyloid deposits, the toxic clumps of misfolded proteins that appear in the brain of affected people. On one hand, microglia may delay the progression of the disease by clearing cellular debris. But it is also possible that they are contributing to disease.

Early synapse loss is a hallmark of many neurodegenerative disorders. Growing evidence points to the possibility that microglial pruning pathways seen in early development may be reactivated later in life, leading to disease. Unpublished data from Stevens’s lab presented at the conference suggest that microglia are involved in the early stages of Alzheimer’s and that blocking microglia’s effects could reduce the synapse loss seen in Huntington’s disease.

As a newly burgeoning field, there are still more questions than answers. Next year’s conference is likely to bring us closer to understanding what these dynamic cells are doing in the brain.

Once the underdogs, microglia may be the key to future therapeutics for a wide variety of psychiatric and neurodegenerative disorders.

Source: Rise of the Microglia By Diana Kwon | October 23, 2015


Microglia represent the endogenous brain defence and immune system, which is responsible for CNS protection against various types of pathogenic factors. Microglial cells derive from progenitors that have migrated from the periphery and are from the mesodermal/ mesenchymal origin. During postnatal development, they immigrate into the brain commonly until postnatal day 10 in rodents. After invading the CNS, microglial precursors disseminate relatively homogeneously throughout the neural tissue and acquire a specific phenotype, which clearly distinguishes them from their precursors, the blood-derived monocytes.

The ´resting´ microglia are the fastest moving cells in the brain.

Under physiological conditions microglia in the CNS exist in the ramified or what was generally termed the ‘resting’ state. The resting microglial cell is characterised by a small cell body and much elaborated thin processes, which send multiple branches and extend in all directions. Similar to astrocytes, every microglial cell has its own territory, about 15 –  30 µm wide; there is very little overlap between neighbouring territories. The processes of resting microglial cells are constantly moving through its territory; this is a relatively rapid movement with a speed of about 1.5 µm/min and thus microglial processes represent the fastest moving structures in the brain. At the same time microglial processes also constantly send out and retract small protrusions, which can grow and shrink by 2–3 µm/min. The microglia seems to be randomly scanning through their domains. Recent studies, however, have demonstrated that these processes rest for periods of minutes at sites of synaptic contacts. Considering the velocity of this movement, the brain parenchyma can be completely scanned by microglial processes every several hours.

The motility of the processes is not affected by neuronal firing, but it is sensitive to activators (ATP and its analogues) and inhibitors of purinoceptors.

Focal neuronal damage induces a rapid and concerted movement of many microglial processes towards the site of lesion, and within less than an hour the latter can be completely surrounded by these processes. This injury-induced motility is also governed, at least in part, by activation of purinoceptors; it is also sensitive to the inhibition of gap junctions, which are present in astrocytes, but not in microglia; inhibition of gap junctions also affects the physiological motility of astroglial processes. Therefore, it appears that astrocytes signal to the microglia by releasing ATP (and possibly some other molecules) through connexin hemichannels.

All in all, microglial processes act as a very sophisticated and fast scanning system. This system can, by virtue of receptors residing in the microglial cell plasmalemma (plasma membrane), immediately detect injury and initiate the process of active response, which eventually triggers the full blown microglial activation.

Activation of microglia

When a brain insult is detected by microglial cells, they launch a specific program that results in the gradual transformation of resting, ramified microglia into an ameboid form; this process is generally referred to as ‘microglial activation’ and proceeds through several steps.

During the first stage of microglial activation resting microglia retract their processes, which become fewer and much thicker, increase the size of their cell bodies, change the expression of various enzymes and receptors, and begin to produce immune response molecules. Some microglial cells return into a proliferative mode, and microglial numbers around the lesion site start to multiply. Microglial cells become motile and using amoeboid-like movements they gather around sites of insult. If the damage persists and CNS cells begin to die, microglial cells undergo further transformation and become phagocytes. This is, naturally, a rather sketchy account of the complex and highly coordinated changes which occur in microglial cells; the process of activation is gradual and most likely many sub-states exist on the way from resting to phagocytic microglia. Furthermore, activated microglial cells may display quite heterogeneous properties in different types of pathologies and in different parts of the brain.

The precise nature of the initial signal that triggers the process of microglial activation is not fully understood; it may be associated either with the withdrawal of some molecules (the ‘off-signal’) released during normal CNS activity or by the appearance of abnormal molecules or abnormal concentrations of otherwise physiologically present molecules (on-signal). Both types of signalling can provide microglia with relevant information about the status of brain parenchyma within their territorial domain.

The ‘off-signals’ that may indicate deterioration in neural networks are not yet fully characterised. A good example of this type of communication are neurotransmitters. Microglial cells express a variety of the classical neurotransmitter receptors such as receptors for GABA, glutamate, dopamine, noradrenaline. In most cases, activation of the receptors counteracts the activation of microglial cells with respect to acquiring a pro-inflammatory phenotype. One might speculate that depression of neuronal activity could affect neighbouring microglia, turning them into an ‘alerted’ state. In fact, these ‘off-signals’ allow microglia to sense disturbance even if the nature of the damaging factor cannot be identified.

The ‘on-signalling’ is conveyed by a wide array of molecules, either associated with cell damage or with foreign matter invading the brain. In particular, damaged neurones can release high amounts of ATP, cytokines, neuropeptides, growth factors. Many of these factors can be sensed by microglia and trigger activation. It might well be that different molecules can activate various subprogrammes of this routine, regulate therefore the speed and degree of microglial activation. Some of these molecules can carry both ‘off’ and ‘on’ signals:


for example, low concentrations of ATP may be indicative of normal ongoing synaptic activity, whereas high concentrations signal cell damage.


Microglia are also capable of sensing disturbances in brain metabolism: for example, accumulation of ammonia, which follows grave metabolic failures (e.g. during hepatic encephalopathy) can activate microglial cells either directly or via intermediates such as NO (Nitric oxide) or ATP.

Spidery microglia, in red. From Kettenmann et al., Neuron 2013


Migration and motility

Microglial migration is essential for many pathophysiological processes, including immune defence and wound healing.

Microglial cells exhibit two types of movement activity:

in the ramified (“resting”) form, they actively move their processes without translocation of the cell body as was already described above.

In the amoeboid form, microglial cells not only move their processes but in addition, the entire cell can migrate through the brain tissue. Microglial migration occurs in development when invading monocytes disseminate through the brain.

Another type of migration is triggered by a pathologic insult when ramified microglia undergoes activation, transform into the amoeboid form and migrate to the site of injury. There are many candidate molecules which may serve as pathological signals and initiate microglial migration and act as chemoattractant molecules. These molecules include ATP, cannabinoids, chemokines, lysophosphatidic acid and bradykinin. The actual movement of microglial cells involves redistribution of salt and water and various ion channels and transporters important for this process. In particular, K+ channels, Cl channels, Na+/H+ exchanger, Cl/HCO3 exchanger, and Na+/HCO3 co-transporter contribute to microglial motility and migration.


The influence of gold surface texture on microglia morphology and activation Microglia seeded on glass, ultra-flat gold (UF-Au), ultra-thin (UT) nanoporous gold (np-Au) np-Au and np-Au monolith were adherent to all surfaces and their viability was not compromised as assessed by multiple toxicity assays.!divAbstract


Microglial cells are the professional innate phagocytes of the CNS tissue.

This function is important for the normal brain, during brain development; in pathology and regeneration.

In the CNS development, microglial phagocytosis is instrumental in removing apoptotic cells and may be involved in synapse removal during development and potentially in pruning synapses in the postnatal brain. Microglial phagocytosis is intimately involved in many neurological diseases. In response to the lesion, microglial cells accumulate at the damaged site and remove cellular debris or even parts of damaged cells.

Through phagocytosis, microglial cells can also accumulate various pathological factors such as for example beta-amyloid in Alzheimer’s disease or myelin fragments in demyelinating diseases. Multiple factors, receptors and signalling cascades can regulate the phagocytic activity. In particular, microglial phagocytosis is controlled by purinoceptors; the metabotropic P2Y6 receptors stimulate whereas ionotropic P2X7 receptors inhibit phagocytotic activity. Microglial phagocytosis is also controlled by the glial-derived neurotrophic factor, by the ciliary neurotrophic factor, by TOLL receptors, by prostanoid receptor etc.


Age-primed microglia hypothesis of Parkinson’s disease. Microglia functions differentially in the young (left) and aged (right) brain. Left: when facing pathogenic stimuli (large black dots), the healthy microglia in the young brain respond by releasing neurotrophic factors (small yellow dots) to support the endangered dopaminergic neurones and limit neuronal damages. Right: in the aged brain oxidative stress and inflammatory factors (small black dots), which damage the vulnerable dopaminergic neurones and eventually lead to neurodegeneration. (From Luo et al.,2010 with permission). Image source

Antigen presentation

Microglial cells are the dominant antigen presenting cells in the central nervous system. Under resting conditions the expression of the molecular complex for presenting antigen, the major histocompatibility complex II (MHCII) and co-stimulatory molecules such as CD80, CD86 and CD40 is below detection. Upon injury, the molecules are highly upregulated and the expression of this complex is essential for interacting with T lymphocytes. This up-regulation has been described in a number of pathologies and is well studied in Multiple Sclerosis. Microglial cells phagocytose myelin, degrade it and present peptides of the myelin proteins as antigens. By releasing cytokines such as CCl2 microglial cells are important for recruiting leukocytes into the CNS. Microglia interacts with infiltrating T lymphocytes, and thus, mediate the immune response in the brain. They have the capacity to stimulate proliferation of both TH1- and TH2-CD4 positive T cells.


microglial and mo-MΦ functions – cascade of events. (a) Resident microglia originates from yolk sac macrophages that repopulate CNS parenchyma during early development and are self-renewed locally, independent from bone marrow-derived monocytes, by the proliferation of primitive progenitors. (b) In the steady state, microglia are constantly scanning their environment through their highly motile processes. These cells facilitate the maintenance of synapses (c) and neurogenesis (d), as well as secrete growth factors essential for normal CNS performance (e). Upon recognition of a danger signal, microglia retracts their branches, become round and ameboid, and convert into an activated mode (f). A short or moderate signal directs microglia toward a neuroprotective phenotype; these cells clear debris by phagocytosis (g), secrete growth factors associated with remyelination (h) and support regeneration (i). Intensive acute or chronic activation renders microglia neurotoxic; under such conditions, microglia fails to acquire a neuroprotective phenotype. Instead, these cells produce reactive oxygen species (ROS), nitric oxide (NO), proteases, and pro-inflammatory cytokines such as IL-1, IL-6, and TNF-α, all of which endanger neuronal activity (j). Microglial malfunction results in the recruitment of mo-MΦ to the damage site (k). mo-MΦ secrete anti-inflammatory cytokines such as IL-10 and TGF-β, express factors associated with an immune resolution such as mannose receptor and arginase 1 (ARG1), and promote neuroprotection and cell renewal (l), all of which are functions that cannot be provided, under these conditions, by the resident microglia.

Signalling pathways implicated in the phagocytosis of neurons and neuronal structures.

Signalling pathways implicated in the phagocytosis of neurones and neuronal structures. Microglial phagocytosis of neurones is regulated by the neuronal presentation and microglial recognition of ‘eat-me’ (left) and ‘don’t eat-me’ (right) signals. However, note that the utilisation of different signals, opsonins and receptors is dependent on the specific (patho)physiological context. Neuronal eat-me signals are recognised by microglial phagocytic receptors either directly or following their binding by opsonins, which are in turn recognised by microglial receptors. Phosphatidylserine that is exposed on neurons can be bound by the opsonins milk fat globule-EGF factor 8 (MFG-E8), growth arrest-specific protein 6 (GAS6) or protein S, which can induce phagocytosis by binding to and activating a vitronectin receptor (VNR) (in the case of MFG-E8) or MER receptor tyrosine kinase (MERTK) (in the case of GAS6 or protein S). Note that stimulation of MERTK can also occur downstream of VNR activation (dashed arrow). Alternatively, neuron-exposed phosphatidylserine may directly bind to brain-specific angiogenesis inhibitor 1 (BAI1) on microglia, and neuron-exposed calreticulin or neuron-bound C1q can induce phagocytosis by activating the microglial low-density lipoprotein receptor-related protein (LRP). C1q can also bind to glycoproteins from which sialic acid residues have been removed by the enzyme neuraminidase. C1q deposition on desialylated glycoproteins, in turn, leads to the conversion of C3 to the opsonin C3b, which activates neuronal phagocytosis via the microglial complement receptor 3 (CR3) and its signalling partner DNAX-activation protein 12 (DAP12). By contrast, neuronal don’t eat-me signals inhibit phagocytosis and can in some instances also suppress inflammation. Neuronal CD47 and sialylated glycoproteins inhibit phagocytosis of neurones by binding to the microglial receptors signal regulatory protein 1α (SIRP1α) and sialic acid binding immunoglobulin-like lectins (SIGLECs), respectively.

Microglial phagocytosis of live cells and neuronal structures.

Microglial phagocytosis of live cells and neuronal structures. The figure illustrates situations in which phagocytic recognition leads to the removal of neuronal structures (synapses and neurites) or live cells (glioma cells, neutrophils, neuronal precursors and stressed-but-viable neurones) in the CNS. The shown pathways have been implicated in mediating phagocytic recognition of each target, but other signals may contribute to these processes. a | During development as well as in the adult animal, weak synapses are removed through a process that is dependent on the complement components C1q and C3 and the microglial complement receptor 3 (CR3). b | During development, microglia phagocytose live neuronal progenitors, and this involves the local release of reactive oxygen and nitrogen species (RONS) by microglia. RONS may induce caspase 3 activation in the targeted neuronal progenitor, which may be phagocytosed via the CR3-subunit CD11b and the adaptor protein DNAX-activation protein 12 (DAP12). c | During brain pathology, sub-toxic neuronal insults (such as inflammation, oxidative stress, excessive levels of glutamate or energy depletion) can induce the reversible exposure of the neuronal eat-me signal phosphatidylserine. Phosphatidylserine is recognised by the opsonin milk fat globule-EGF factor 8 (MFG-E8), which induces phagocytosis through activation of the microglial vitronectin receptor (VNR). In addition, MER receptor tyrosine kinase (MERTK)9 also contributes to phagocytic signalling under these circumstances, either through its activation downstream of VNR or through the recognition of unidentified opsonins or eat-me signals. d,e | In addition to the removal of neurones, neuronal precursors and neuronal structures, microglia can phagocytose live neutrophils through activation of the microglial VNR and lectins, or live glioma cells19 through microglial sialic acid binding immunoglobulin-like lectin-H (SIGLEC-H) and DAP12.

Mechanisms mediating microglial phagocytosis of stressed-but-viable neurons during inflammation.

Mechanisms mediating microglial phagocytosis of stressed-but-viable neurones during inflammation. Activation of microglial Toll-like receptor 2 (TLR2) and TLR4 by damage- or pathogen-associated molecules or by amyloid-β results in the release of reactive oxygen and nitrogen species (RONS) derived from inducible nitric oxide synthase (iNOS) and NADPH oxidase (PHOX). RONS can cause nearby neurones to expose phosphatidylserine in a reversible manner on their surface5 through the stimulation of a phosphatidylserine scramblase (probably a TMEM16 protein26) and/or the inhibition of a phosphatidylserine translocase (probably type 4 P-type ATPases (P4-ATPases) ATP8A1 or ATP8A2 ). Neuronal stress induced by activated microglia or by other means may also cause exposure of phosphatidylserine on stressed-but-viable neurons via calcium- or RONS-mediated activation of a scramblase or inhibition of a translocase, via ATP depletion-induced inhibition of translocase or, in some circumstances, via caspase-mediated activation of a distinct scramblase (probably XK-related protein 8 (XKR8)). Exposed phosphatidylserine is bound by milk fat globule-EGF factor 8 (MFG-E8), which is released by activated microglia and astrocytes and which promotes phagocytosis of the phosphatidylserine-tagged neurone through the vitronectin receptor (VNR). The VNR may drive phagocytosis by triggering actin polymerization in synergy with MER receptor tyrosine kinase (MERTK). MERTK is upregulated by microglia activation and may also bind to neurones via opsonins that bind exposed phosphatidylserine or other eat-me signals.

—Summary Of Evidence —

That Molecular Pathways Characterised In Pathology Are Also Utilised By MICROGLIA —-

In The Normal And Developing Brain To Influence Synaptic Development And Connectivity,

And Therefore Should Become Targets Of Future Research

Microglia: New Roles for the Synaptic Stripper

Neurone: Volume 77, Issue 1, 9 January 2013, Pages 10–18

Helmut Kettenmann(1), Frank Kirchhoff(2), Alexei Verkhratsky(3, 4)

  • 1 Max-Delbrück-Center for Molecular Medicine, 13125 Berlin, Germany
  • 2 Department of Molecular Physiology, University of Saarland, 66424 Homburg, Germany
  • 3 Faculty of Life Sciences, The University of Manchester, Manchester M13 9PL, UK
  • 4 Achucarro Center for Neuroscience, Ikerbasque, Basque Foundation for Science, 48011 Bilbao, Spain

For more details

Physiology of Microglia

Helmut Kettenmann, Uwe-Karsten Hanisch, Mami Noda, Alexei Verkhratsky
  1. Matthew R. Ritter, Eyal Banin, Stacey K., Moreno, Edith Aguilar, Michael I, Dorrell, and Martin Friedlander.  Myeloid progenitors differentiate into microglia and promote vascular repair in a model of ischemic retinopathy: J Clin Invest. 2006 Dec 1; 116(12): 3266–3276. Vision loss associated with ischemic diseases such as retinopathy of prematurity and diabetic retinopathy are often due to retinal neovascularization. While significant progress has been made in the development of compounds useful for the treatment of abnormal vascular permeability and proliferation, such therapies do not address the underlying hypoxia that stimulates the observed vascular growth. Using a model of oxygen-induced retinopathy, we demonstrate that a population of adult BM–derived myeloid progenitor cells migrated to avascular regions of the retina, differentiated into microglia, and facilitated normalisation of the vasculature. Myeloid-specific hypoxia-inducible factor 1α (HIF-1α) expression was required for this function, and we also demonstrate that endogenous microglia participated in retinal vascularization. These findings suggest what we believe to be a novel therapeutic approach for the treatment of ischemic retinopathies that promotes vascular repair rather than destruction.
  2. Judy Choi, Qingdong Zheng, Howard E. Katz, Tomás R., Guilarte. Silica-Based Nanoparticle Uptake and Cellular Response by Primary Microglia: Environ Health Perspect 118:589-595 (2010). [online 21 December 2009]    Silica nanoparticles (SiNPs) are being formulated for cellular imaging and for nonviral gene delivery in the central nervous system (CNS), but it is unclear what potential effects SiNPs can elicit once they enter the CNS. As the resident macrophages of the CNS, microglia are the cells most likely to respond to SiNP entry into the brain. Upon activation, they are capable of undergoing morphological and functional changes.  This is the first study demonstrating the in vitro effects of SiNPs in primary microglia. Our findings suggest that very low levels of SiNPs are capable of altering microglial function. Increased reactive oxygen species (ROS) and reactive nitrogen species (RNS) production, changes in proinflammatory genes, and cytokine release may not only adversely affect microglial function but also affect surrounding neurones.
  3. Yang Zhan, Rosa C Paolicelli, Francesco Sforazzini et al. Deficient neuron-microglia signalling results in impaired functional brain connectivity and social behaviour: Nature Neuroscience; March 2104; vol. 17; number 3; pg 400-406. In summary, our findings reveal a role for microglia in promoting the maturation of circuit connectivity during development, with synapse elimination going hand in hand with enhanced synaptic multiplicity. Our data support the hypothesis that microglia-mediated synaptic pruning during development has a critical role in sculpting neural circuit function, which may contribute to the physiological and behavioural features of a range of neurodevelopmental disorders. Our data also opens the possibilty that genetic and environmental risk factors for such disorders may exert their effect by modulating synapse elimination. Further studies are warranted to test the hypothesis that variation in synaptic pruning may underlie individual differences in human brain wiring.
  4. Juan I. Rodriguez, Janet K. Kern. Evidence of microglial activation in autism and its possible role in brain underconnectivity. Neuron Glia Biol. 2011 May; 7(2-4): 205–213. Evidence indicates that children with autism spectrum disorder (ASD) suffer from an ongoing neuroinflammatory process in different regions of the brain involving microglial activation. When microglia remain activated for an extended period, the production of mediators is sustained longer than usual and this increase in mediators contributes to loss of synaptic connections and neuronal cell death. Microglial activation can then result in a loss of connections or underconnectivity. Underconnectivity is reported in many studies in autism. One way to control neuroinflammation is to reduce or inhibit microglial activation. It is plausible that by reducing brain inflammation and microglial activation, the neurodestructive effects of chronic inflammation could be reduced and allow for improved developmental outcomes. Future studies that examine treatments that may reduce microglial activation and neuroinflammation, and ultimately help to mitigate symptoms in ASD, are warranted.

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    This diagram shows the relationships and interplay between microglial activation and the neuropathology, medical issues and symptoms in ASD.

  5. Anat London, Merav Cohen and Michal Schwartz. Microglia and monocyte-derived macrophages: functionally distinct populations that act in concert in CNS plasticity and repair.  Front. Cell. Neurosci., 08 April 2013 |
  6. Carmelina Gemma and Adam D. Bachstetter. The role of microglia in adult hippocampal neurogenesis. Front. Cell. Neurosci., 22 November 2013 |
  7. Sabine Hellwig, Annette Heinrich and Knut Biber. The brain’s best friend: microglial neurotoxicity revisited. Front. Cell. Neurosci., 16 May 2013 |
  8. Peter Thériault, Ayman ElAli and Serge Rivest. The dynamics of monocytes and microglia in Alzheimer’s disease. Alzheimer’s Research & Therapy 2015, 7:41 doi:10.1186/s13195-015-0125-2      The present review summarises current knowledge on the role of monocytes and microglia in AD and how these cells can be mobilised to prevent and treat the disease.
  9. Guy C. Brown & Jonas J. Neher. Microglial phagocytosis of live neurones. Nature Reviews Neuroscience 15, 209–216 (2014) doi:10.1038/nrn3710
    Published online 20 March 2014.
  10. Neuropathology. APPLIED NEUROCYTOLOGY AND BASIC REACTIONS. Dimitri P. Agamanolis, M.D. 
  11. Rosa C. Paolicelli, Giulia Bolasco, Francesca Pagani et al. Synaptic Pruning by Microglia Is Necessary for Normal Brain Development. Published Online July 21, 2011. Science 9 September 2011: Vol. 333 no. 6048 pp. 1456-1458
    DOI: 10.1126/science.1202529
  12. Axel Nimmerjahn, Frank Kirchhoff, Fritjof Helmchen. Resting Microglial Cells Are Highly Dynamic Surveillants of Brain Parenchyma in Vivo. Published Online April 14, 2005. Science 27 May 2005: Vol. 308 no. 5726 pp. 1314-1318. DOI: 10.1126/science.1110647
  13. Hiroaki Wake, Andrew J. Moorhouse, Shozo Jinno, Shinichi Kohsaka, and Junichi Nabekura. Resting Microglia Directly Monitor the Functional State of Synapses In Vivo and Determine the Fate of Ischemic Terminals. The Journal of Neuroscience, 1 April 2009, 29(13): 3974-3980; doi: 10.1523/JNEUROSCI.4363-08.2009. In summary, we report direct, activity-dependent connections between microglia and synapses and have quantified the kinetics of this interaction. These interactions are very consistent in the control brain but markedly prolonged in the ischemic brain. We propose that microglia detects the functional state of the synapses, responding with prolonged contact under pathological conditions. Such prolonged contact is followed on some occasions by synapse elimination, suggesting that microglia are perhaps either attempting to restore synapse function or initiating their subsequent removal (as illustrated schematically in supplemental Fig. 3, available at as supplemental material). Such microglial diagnosis of synapse function is likely to be important in any subsequent remodelling of neuronal circuits after brain injury and provides a novel target for the development of new therapies to improve the recovery of neuronal function after brain damage.
  14. Sarah E. Schipul, Timothy A. Keller, and Marcel Adam Just. Inter-Regional Brain Communication and It’s Disturbance in Autism. Front Syst Neurosci. 2011; 5: 10.
    Published online 2011 Feb 22. doi: 10.3389/fnsys.2011.00010     Recent findings of atypical patterns in both functional and anatomical connectivity in autism have established that autism is a not a localised neurological disorder, but one that affects many parts of the brain in many types of thinking tasks. fMRI studies repeatedly find evidence of decreased coordination between frontal and posterior brain regions in autism, as measured by functional connectivity. Furthermore, neuroimaging studies have also shown evidence of an atypical pattern of frontal white matter development in autism. These findings indicate that limitations of brain connectivity give rise to the varied behavioural deficits found in autism. As research continues to explore these biological mechanisms, new intervention methods may be developed to help improve brain connectivity and overcome the behavioural impairments of autism.
  15. Noël C. Derecki, James C. Cronk, Zhenjie Lu, Eric Xu, Stephen B. G. Abbott, Patrice G. Guyenet & Jonathan Kipnis. Wild-type microglia arrests pathology in a mouse model of Rett syndrome. Nature 484, 105–109 (05 April 2012) doi:10.1038/nature10907
  16. Jieqi Wang, Jan-Eike Wegener, Teng-Wei Huang, Smitha Sripathy, Hector De Jesus-Cortes, Pin Xu, Stephanie Tran, Whitney Knobbe, Vid Leko, Jeremiah Britt, Ruth Starwalt, Latisha McDaniel, Chris S. Ward, Diana Parra, Benjamin Newcomb, Uyen Lao, Cynthia Nourigat, David A. Flowers, Sean Cullen, Nikolas L. Jorstad, Yue Yang, Lena Glaskova, Sébastien Vigneau, Julia Kozlitina, Michael J. Yetman et al. Wild-type microglia do not reverse pathology in mouse models of Rett syndrome. Nature 521, E1–E4 (21 May 2015) doi:10.1038/nature14444

Emerging Field Of Quantum Biology – Interaction Between Quantum Mechanics and Nature (Biology)


According to quantum biology, the European robin has a ‘sixth sense’ in the form of a protein in its eye sensitive to the orientation of the Earth’s magnetic field, allowing it to ‘see’ which way to migrate. Photograph: Helmut Heintges/ Helmut Heintges/Corbis

Learning from nature is an idea as old as mythology — but until now, no one has imagined that the natural world has anything to teach us about the quantum world.

Before the twentieth century, biology and physics rarely crossed paths. Biological systems were often seen as too complex to be penetrable with mathematical methods. After all, how could a set of differential equations or physical principles shed light on something as complex as a living being?

In the early twentieth century, with the advent of more powerful microscopes and techniques, researchers began to delve more deeply into possible physical and mathematical descriptions of microscopic biological systems. Some famous examples (among many) include Turing patterns and morphogenesis, and Schrödinger’s lecture series and book     ‘What is Life?’, [Schrödinger, E. What is Life? (Cambridge Univ. Press, 1992)] in which he predicted several of the functional features of DNA. [ Davies, P. C. W. Quantum Aspects of Life (Imperial College Press, 2008).] The pace of progress in this field is now rapid, and many branches of physics and mathematics have found applications in biology; from the statistical methods used in bioinformatics, to the mechanical and factory-like properties observed at the microscale within cells.[Longuet-Higgins, H. C. Quantum mechanics and biology. Biophys. J. 2, 207215 (1962).]

This progress leads naturally to the question:

Can quantum mechanics play a role in biology?

In many ways it is clear that it already does. Every chemical process relies on quantum mechanics. However, in many ways quantum mechanics is still a concept alien to biology, especially on a scale that can have a physiological impact.[ Wolynes, P. G. Some quantum weirdness in physiology. Proc. Natl Acad. Sci. USA 106,1724717248 (2009)].

Recent technological progress in physics in harnessing quantum mechanics for information processing and encryption puts the question in a different light:

Are there any biological systems that use quantum mechanics to perform a task that either cannot be done classically, or can do that task more efficiently than even the best classical equivalent?

In other words, do some organisms take advantage of quantum mechanics to gain an advantage over their competitors?

Many attempts to find examples of such phenomenon have been met with fierce criticism by both physicists and biologists. [Tegmark, M. Importance of quantum decoherence in brain processes. Phys. Rev. E 61, 4194–4206 (2000)][McKemmish, L. K., Reimers, J. R., McKenzie, R. H., Mark, A. E. & Hush, N. S. Penrose–Hameroff orchestrated objective-reduction proposal for human consciousness is not biologically feasible. Phys. Rev. E 80, 021912 (2009)].

However, over the past decade a range of experiments have suggested that there may be some cases in which quantum mechanics is harnessed for a biological advantage.

Artificial photosynthesis Plants have had millions of years to improve upon photosynthesis, and most green plants are fairly efficient at it, locking down up to 6 percent of the solar energy that strikes a leaf’s surface. Modern solar PV systems can achieve three times higher efficiency. Nonetheless, artificial systems that mimic natural photosynthesis typically don’t provide direct electrical output, as does solar PV. Instead, they use readily available water sources to create a stream of hydrogen that can be stored and burned as fuel. Exploring natural photosynthesis helps tease out the secrets plants have as model systems for larger fuel production. According to Thomas J. Meyer, Arey Distinguished Professor of Chemistry at the University of North Carolina, Chapel Hill, “The goal of artificial photosynthesis is to mimic the green plants and other photosynthetic organisms in using sunlight to make high-energy chemicals but with far higher efficiencies and simplicity of design for scale-up and large-scale production.” Photosynthesis begins when the pigments within a plant cell act as antennas that capture photons. These antennas then generate electrons that pass the energy along to other molecules in the multistep process of energy capture, redirection and storage. One or two types of pigments are necessary for a completely functional system: Photosystem I refers to the absorption of light via the main type of chlorophyll by itself. Photosystem II requires a second pigment. Light-harvesting polymers must be able to absorb sunlight over a significant span of the spectrum as well, in order to not waste photons. To compete with solar PV and other green energy systems, artificial photosynthesis research is leaning toward maximizing the efficiency of photon absorption. Generally, the way to do this is to find or develop materials that are easy and inexpensive to produce. Decades ago, Japan’s Akira Fujishima published research on the ability of titanium dioxide (TiO2) to split water molecules into their constituent oxygen and hydrogen atoms when exposed to light. Since Fujishima’s report, interest in TiO2 has languished because it is a relatively poor absorber of visible light. Still, researchers from the Pennsylvania State University in University Park, Arizona State University in Tempe, and the University of North Texas in Denton, U.S.A., have collaborated to improve TiO2-based systems.

In what form do these quantum effects usually appear?

In quantum information, arguably the most important quantum effect is that quantum bits can exist in superpositions whereas classical bits cannot. In quantum biology, the role of quantum effects can be subtle. However, we may consider a biological system that exploits coherent superpositions of states for some practical purpose to be the clearest example of functional quantum biology. [Neill Lambert, Yueh-Nan Chen, Yuan-Chung Cheng, Che-Ming Li, Guang-Yin Chen & Franco Nori; Quantum biology: Nature Physics 9,10–18(2013) doi:10.1038/nphys2474]

Are we ready for quantum biology?

Stomata: does entanglement play a part in plant biology? (Image: Power And Syred/Science Photo Library)

Are we ready for quantum biology?

Are we ready for quantum biology?

In Life on the Edge, Jim Al-Khalili and Johnjoe McFadden argue quantum effects are decisive in biology – but this challenging idea needs more proof.

FOR 15 years, theoretical physicist Jim Al-Khalili and molecular geneticist Johnjoe McFadden have been discussing how quantum physics, the science of the incredibly small, might affect biology.

Quantum physics and biology have long been regarded as unrelated disciplines, describing nature at the inanimate microlevel on the one hand and living species on the other hand. Over the past decades the life sciences have succeeded in providing ever more and refined explanations of macroscopic phenomena that were based on an improved understanding of molecular structures and mechanisms. Simultaneously, quantum physics, originally rooted in a world-view of quantum coherences, entanglement, and other nonclassical effects, has been heading toward systems of increasing complexity.

While in the days of Darwin and Mendel the life sciences were mainly focusing on botany or zoology, modern biology, pharmacology, and medicine are deeply rooted in a growing understanding of molecular interactions and organic information processing.

Quantum physics, on the other hand, was initially centered on microscopic phenomena with photons, electrons, and atoms. But objects of increasing complexity have attracted a growing scientific interest, and since the size scales of both physics and the life sciences have approached each other, it is now very natural to ask: what is the role of quantum physics in and for biology?

Erithacus rubecula, Arabidopsis thaliana

The magnetic compass of the European robin (Erithacus rubecula) has been extensively studied by Wiltschko et al. and others. Magnetic field effects in plants (Arabidopsis thaliana) have also been observed. A radical pair mechanism within the protein cryptochrome may underlie both phenomena.

Erwin Schrödinger, most famous for his wave equation for nonrelativistic quantum mechanics, already ventured across the disciplines in his lecture series “What is life?” (Schrödinger, 1944). He anticipated a molecular basis for human heredity, which was later confirmed to be the DNA molecule (Watson and Crick, 1953). Since the early days of quantum physics, its influence on biology has always been present in a reductionist sense: quantum physics and electrodynamics shape all molecules and thus determine molecular recognition, the workings of proteins, and DNA. Also van der Waals forces, discrete molecular orbitals, and the stability of matter: all this is quantum physics and a natural basis for life and everything we see.

But even 100 years after its development, quantum physics is still a conceptually challenging model of nature: it is often acclaimed to be the most precisely verified theory of nature and yet its common interpretation stands in discrepancy to our classical, i.e., prequantum, world-view, and our natural ideas about reality or space-time. Is there a transition between quantum physics and our everyday world? And how will the life sciences then fit into the picture—with objects covering anything from molecules up to elephants, mammoth trees, or the human brain?

Still half a century ago, the topic had some rather skeptical reviews (Longuet-Higgins, 1962). But experimental advances have raised a new awareness and several recent reviews (e.g., Abbot et al., 2008) sketch a more optimistic picture that may be overoptimistic in some aspects.

[Quantum physics meets biology: Markus Arndt, Thomas Juffmann, and Vlatko Vedral. HFSP J. 2009 Dec; 3(6): 386–400. Published online 2009 Nov 9. doi: 10.2976/1.3244985 PMCID: PMC2839811]

What is Quantum Mechanics ? The weird world of quantum mechanics.

Quantum mechanics is the science of the very small: the body of scientific principles that explains the behaviour of matter and its interactions with energy on the scale of atoms and subatomic particles.

Quantum mechanics starts with the simple idea that energy does not come in just any amount; it comes in discrete chunks, called quanta. But deeper into the theory, some truly surprising – and useful – effects crop up

Superposition: A particle exists in a number of possible states or locations simultaneously – strictly, an electron might be in the tip of your finger and in the furthest corner of the Universe at the same time. It is only when we observe the particle that it ‘chooses’ one particular state.
Entanglement: Two particles can become entangled so that their properties depend on each other – no matter how far apart they get. Under quantum rules, no matter how far apart an “entangled” pair of particles gets, each seems to “know” what the other is up to – they can even seem to pass information to one another faster than the speed of light. A measurement of one seems to affect the measurement of the other instantaneously – an idea even Einstein called “spooky”.
Tunnelling: A particle can break through an energy barrier, seeming to disappear on one side of it and reappear on the other. Lots of modern electronics and imaging depends on this effect.

Experiments suggest this is going on within single molecules in birds’ eyes, and John Morton of University College London explained that the way birds sense it could be stranger still.

“You could think about that as… a kind of ‘heads-up display’ like what pilots have: an image of the magnetic field… imprinted on top of the image that they see around them,” he said.

The idea continues to be somewhat controversial – as is the one that your nose might be doing a bit of quantum biology.

Most smell researchers think the way that we smell has to do only with the shapes of odour molecules matching those of receptors in our noses.

But Dr Turin ( Luca Turin of the Fleming Institute in Greece) believes that the way smell molecules wiggle and vibrate is responsible – thanks to the quantum effect called tunnelling. The idea holds that electrons in the receptors in our noses disappear on one side of a smell molecule and reappear on the other, leaving a little bit of energy behind in the process.

A paper published in Plos One this shows that people can tell the difference between two molecules of identical shape but with different vibrations, suggesting that shape is not the only thing at work. Simon Gane, a researcher at the Royal National Throat, Nose and Ear Hospital and lead author of the Plos One paper, said that the tiny receptors in our noses are what are called G-protein coupled receptors. “They’re a sub-family of the receptors we have on all cells in our body – they’re the targets of most drug development,” he explained. “What if – and this is a very big if – there’s a major form of receptor-drug interaction that we’re just not noticing because we’re not looking for a quantum effect? That would have profound implications for drug development, design and discovery.”

What intrigues all these researchers is how much more quantum trickery may be out there in nature.

“Are these three fields the tip of the iceberg, or is there actually no iceberg underneath?” asked Dr Turin. “We just don’t know. And we won’t know until we go and look.”

Jim Al-Khalili of the University of Surrey is investigating whether tunnelling occurs during mutations to our DNA – a question that may be relevant to the evolution of life itself, or cancer research.

He told the BBC: “If quantum tunnelling is an important mechanism in mutations, is quantum mechanics going to somehow answer some of the questions about how a cell becomes cancerous?”

“And suddenly you think, ‘Wow!’ Quantum mechanics is not just a crazy side issue or a fringe field where some people are looking at some cranky ideas. If it really might help answer some of the very big questions in science, then it’s hugely important.”


Classical physics explains matter and energy on a scale familiar to human experience, including the behaviour of astronomical bodies. It remains the key to measurement for much of modern science and technology. However, towards the end of the 19th century, scientists discovered phenomena in both the large (macro) and the small (micro) worlds that classical physics could not explain. As Thomas Kuhn explains in his analysis of the philosophy of science, The Structure of Scientific Revolutions, coming to terms with these limitations led to two major revolutions in physics which created a shift in the original scientific paradigm: the theory of relativity and the development of quantum mechanics.

In this sense, the word ‘quantum’ means the minimum amount of any physical entity involved in an interaction. Certain characteristics of matter can take only discrete values.

Light behaves in some respects like particles and in other respects like waves.

Matter—particles such as electrons and atoms—exhibits wavelike behaviour too. Some light sources, including neon lights, give off only certain discrete frequencies of light. Quantum mechanics shows that light, along with all other forms of electromagnetic radiation, comes in discrete units, called photons, and predicts its energies, colours, and spectral intensities.

Some aspects of quantum mechanics can seem counterintuitive or even paradoxical, because they describe behaviour quite different from that seen at larger length scales. In the words of Richard Feynman, quantum mechanics deals with “nature as She is – absurd”. For example, the uncertainty principle of quantum mechanics means that the more closely one pins down one measurement (such as the position of a particle), the less precise another measurement pertaining to the same particle (such as its momentum) must become.

  • At Massachusetts Institute of Technology, Mass., U.S.A., Daniel Nocera and his colleagues have produced an

    The structure of an artificial leaf produced by researcher Daniel Nocera’s team features a silicon junction that captures photons. The cobalt-based oxygen evolving complex (Co-OEC) and a nickel, molybdenum and zinc alloy (NiMoZn) perform the water-splitting function and transport the captured energy into storage.

    artificial leaf made mostly of silicon, nickel and cobalt. The leaf is the size of a playing card, and it is about ten times more efficient than a natural leaf and can operate continuously for about 45 hours.When the layered leaf is exposed to light and water simultaneously, a silicon junction captures incoming photons and energizes the cobalt-based oxygen evolving complex at one end and a nickel, molybdenum and zinc alloy at the other. Together, they split the water touching the device and produce hydrogen that can be put into storage. Oxygen is released from the cobalt side of the leaf, and hydrogen gas from the nickel-molybdenum-zinc side. Separating the two sides while the gases are produced would produce ample hydrogen for fuel cells.Previously, platinum was the catalyst of choice for creating the electrolytic effect, but the nickel-molybdenum-zinc alloy performs more than adequately while being much less expensive.

Consequences of the light being quantised

Why Ultraviolet Light can cause sunburn but visible or infrared light cannot ?

The relationship between the frequency of electromagnetic radiation and the energy of each individual photon is why ultraviolet light can cause sunburn, but visible or infrared light cannot. A photon of ultraviolet light will deliver a high amount of energy – enough to contribute to cellular damage such as occurs in a sunburn. A photon of infrared light will deliver a lower amount of energy – only enough to warm one’s skin. So, an infrared lamp can warm a large surface, perhaps large enough to keep people comfortable in a cold room, but it cannot give anyone a sunburn.
All photons of the same frequency have identical energy, and all photons of different frequencies have proportionally different energies. However, although the energy imparted by photons is invariant at any given frequency, the initial energy state of the electrons in a photoelectric device prior to absorption of light is not necessarily uniform. Anomalous results may occur in the case of individual electrons. For instance, an electron that was already excited above the equilibrium level of the photoelectric device might be ejected when it absorbed uncharacteristically low frequency illumination. Statistically, however, the characteristic behaviour of a photoelectric device will reflect the behaviour of the vast majority of its electrons, which will be at their equilibrium level. This point is helpful in comprehending the distinction between the study of individual particles in quantum dynamics and the study of massed particles in classical physics.


For years biologists have been wary of applying the strange world of quantum mechanics, where particles can be in two places at once or connected over huge distances, to their own field. But it can help to explain some amazing natural phenomena we take for granted.

Every year, around about this time, thousands of European robins, Erithacus rubecula, escape the oncoming harsh Scandinavian winter and head south to the warmer Mediterranean coasts. How they find their way unerringly on this 2,000-mile journey is one of the true wonders of the natural world. For unlike many other species of migratory birds, marine animals and even insects, they do not rely on landmarks, ocean currents, the position of the sun or a built-in star map. Instead, they are among a select group of animals that use a remarkable navigation sense – remarkable for two reasons.

The first is that they are able to detect tiny variations in the direction of the Earth’s magnetic field – astonishing in itself, given that this magnetic field is 100 times weaker than even that of a measly fridge magnet. The second is that robins seem to be able to “see” the Earth’s magnetic field via a process that even Albert Einstein referred to as “spooky”. The birds’ in-built compass appears to make use of one of the strangest features of quantum mechanics.

Over the past few years, the European robin, and its quantum “sixth sense”, has emerged as the pin-up for a new field of research, one that brings together the wonderfully complex and messy living world and the counter-intuitive, ethereal but strangely orderly world of atoms and elementary particles in a collision of disciplines that is as astonishing and unexpected as it is exciting.

Welcome to the new science of quantum biology.

Most people have probably heard of quantum mechanics, even if they don’t really know what it is about. Certainly, the idea that it is a baffling and difficult scientific theory understood by just a tiny minority of smart physicists and chemists has become part of popular culture. Quantum mechanics describes a reality on the tiniest scales that is, famously, very weird indeed; a world in which particles can exist in two or more places at once, spread themselves out like ghostly waves, tunnel through impenetrable barriers and even possess instantaneous connections that stretch across vast distances.

But despite this bizarre description of the basic building blocks of the universe, quantum mechanics has been part of all our lives for a century. Its mathematical formulation was completed in the mid-1920s and has given us a remarkably complete account of the world of atoms and their even smaller constituents, the fundamental particles that make up our physical reality. For example, the ability of quantum mechanics to describe the way that electrons arrange themselves within atoms underpins the whole of chemistry, material science and electronics; and is at the very heart of most of the technological advances of the past half-century. Without the success of the equations of quantum mechanics in describing how electrons move through materials such as semiconductors we would not have developed the silicon transistor and, later, the microchip and the modern computer.

However, if quantum mechanics can so beautifully and accurately describe the behaviour of atoms with all their accompanying weirdness, then why aren’t all the objects we see around us, including us – which are after all only made up of these atoms – also able to be in two place at once, pass through impenetrable barriers or communicate instantaneously across space?

One obvious difference is that the quantum rules apply to single particles or systems consisting of just a handful of atoms, whereas much larger objects consist of trillions of atoms bound together in mind-boggling variety and complexity. Somehow, in ways we are only now beginning to understand, most of the quantum weirdness washes away ever more quickly the bigger the system is, until we end up with the everyday objects that obey the familiar rules of what physicists call the “classical world”.

In fact, when we want to detect the delicate quantum effects in everyday-size objects we have to go to extraordinary lengths to do so – freezing them to within a whisker of absolute zero and performing experiments in near-perfect vacuums.

Quantum effects were certainly not expected to play any role inside the warm, wet and messy world of living cells, so most biologists have thus far ignored quantum mechanics completely, preferring their traditional ball-and-stick models of the molecular structures of life.

Meanwhile, physicists have been reluctant to venture into the messy and complex world of the living cell; why should they, when they can test their theories far more cleanly in the controlled environment of the lab where they at least feel they have a chance of understanding what is going on?

Yet, 70 years ago, the Austrian Nobel prize-winning physicist and quantum pioneer, Erwin Schrödinger, suggested in his famous book, What is Life?, that, deep down, some aspects of biology must be based on the rules and orderly world of quantum mechanics. His book inspired a generation of scientists, including the discoverers of the double-helix structure of DNA, Francis Crick and James Watson. Schrödinger proposed that there was something unique about life that distinguishes it from the rest of the non-living world. He suggested that, unlike inanimate matter, living organisms can somehow reach down to the quantum domain and utilise its strange properties in order to operate the extraordinary machinery within living cells.


Erwin Schrödinger, whose book What is Life? suggested that the macroscopic order of life was based on order at its quantum level. Photograph: Bettmann/CORBIS

  • Schrödinger’s argument was based on the paradoxical fact that the laws of classical physics, such as those of Newtonian mechanics and thermodynamics, are ultimately based on disorder. Consider a balloon. It is filled with trillions of molecules of air all moving entirely randomly, bumping into one another and the inside wall of the balloon. Each molecule is governed by orderly quantum laws, but when you add up the random motions of all the molecules and average them out, their individual quantum behaviour washes out and you are left with the gas laws that predict, for example, that the balloon will expand by a precise amount when heated. This is because heat energy makes the air molecules move a little bit faster, so that they bump into the walls of the balloon with a bit more force, pushing the walls outward a little bit further. Schrödinger called this kind of law “order from disorder” to reflect the fact that this apparent macroscopic regularity depends on random motion at the level of individual particles.

But what about life? Schrödinger pointed out that many of life’s properties, such as heredity, depend of molecules made of comparatively few particles – certainly too few to benefit from the order-from-disorder rules of thermodynamics. But life was clearly orderly.

Where did this orderliness come from?

Schrödinger suggested that life was based on a novel physical principle whereby its macroscopic order is a reflection of quantum-level order, rather than the molecular disorder that characterises the inanimate world. He called this new principle “order from order”.

But was he right?

Up until a decade or so ago, most biologists would have said no. But as 21st-century biology probes the dynamics of ever-smaller systems – even individual atoms and molecules inside living cells – the signs of quantum mechanical behaviour in the building blocks of life are becoming increasingly apparent. Recent research indicates that some of life’s most fundamental processes do indeed depend on weirdness welling up from the quantum undercurrent of reality.

Here are a few of the most exciting examples.

Enzymes are the workhorses of life. They speed up chemical reactions so that processes that would otherwise take thousands of years proceed in seconds inside living cells. Life would be impossible without them. But how they accelerate chemical reactions by such enormous factors, often more than a trillion-fold, has been an enigma. Experiments over the past few decades, however, have shown that enzymes make use of a remarkable trick called quantum tunnelling to accelerate biochemical reactions. Essentially, the enzyme encourages electrons and protons to vanish from one position in a biomolecule and instantly re-materialise in another, without passing through the gap in between – a kind of quantum teleportation.

[I believe,(although I do not have any proof or reference for it) it might be following the same physics principles, as is followed by an electrons that travels through a wire, when a potential is applied across it. The electron seems to be travelling at light speed although, what happens actually is that, as soon as an electron enters one end of wire, at the same time, at the other end of the wire, an electron which was initially part of wire itself ejects simultaneously.Now the time required for the electron to be ejected depends upon the electric potential applied across and the material of the wire itself.]

  • Quantum tunnelling (or tunneling) is the quantum-mechanical effect of transitioning through a classically-forbidden energy state. It can be generalized to other types of classically-forbidden transitions as well.

    Consider rolling a ball up a hill. If the ball is not given enough velocity, then it will not roll over the hill. This scenario makes sense from the standpoint of classical mechanics, but is an inapplicable restriction in quantum mechanics simply because quantum mechanical objects do not behave like classical objects such as balls. On a quantum scale, objects exhibit wavelike behaviour.               For a quantum particle moving against a potential energy “hill”, the wave function describing the particle can extend to the other side of the hill. This wave represents the probability of finding the particle in a certain location, meaning that the particle has the possibility of being detected on the other side of the hill. This behaviour is called tunneling; it is as if the particle has ‘dug’ through the potential hill.

    As this is a quantum and non-classical effect, it can generally only be seen in nanoscopic phenomena — where the wave behaviour of particles is more pronounced.

And before you throw your hands up in incredulity, it should be stressed that quantum tunnelling is a very familiar process in the subatomic world and is responsible for such processes as radioactive decay of atoms and even the reason the sun shines (by turning hydrogen into helium through the process of nuclear fusion). Enzymes have made every single biomolecule in your cells and every cell of every living creature on the planet, so they are essential ingredients of life. And they dip into the quantum world to help keep us alive.

Another vital process in biology is of course photosynthesis. Indeed, many would argue that it is the most important biochemical reaction on the planet, responsible for turning light, air, water and a few minerals into grass, trees, grain, apples, forests and, ultimately, the rest of us who eat either the plants or the plant-eaters.

The initiating event is the capture of light energy by a chlorophyll molecule and its conversion into chemical energy that is harnessed to fix carbon dioxide and turn it into plant matter. The process whereby this light energy is transported through the cell has long been a puzzle because it can be so efficient – close to 100% and higher than any artificial energy transport process.

Summary of Quantum Processes required for ATP synthesis The figure presents the scheme of the integral membrane proteins forming the photosynthetic unit. Light-absorption and excitation transfer within the light-harvesting proteins (LH-II and LH-I) are represented by wavy lines. Electron transfer within the photosynthetic reaction center (RC), cytochrome c2, and bc1 complex is represented by blue lines. Proton transfer in the bc1 complex and the ATPase is represented by red lines. The chemical reaction of ATP synthesis is represented by a black line.

qubiot_schemeThe first step in photosynthesis is the capture of a tiny packet of energy from sunlight that then has to hop through a forest of chlorophyll molecules to makes its way to a structure called the reaction centre where its energy is stored. The problem is understanding how the packet of energy appears to so unerringly find the quickest route through the forest. An ingenious experiment, first carried out in 2007 in Berkley, California, probed what was going on by firing short bursts of laser light at photosynthetic complexes. The research revealed that the energy packet was not hopping haphazardly about, but performing a neat quantum trick. Instead of behaving like a localised particle travelling along a single route, it behaves quantum mechanically, like a spread-out wave, and samples all possible routes at once to find the quickest way.

Radical Pair

Schematic illustration of a bird’s eye and its important components. The retina (a) converts images from the eye’s optical system into electrical signals sent along the ganglion cells forming the optic nerve to the brain. (b) An enlarged retina segment is shown schematically. (c) The retina consists of several cell layers. The primary signals arising in the rod and cone outer segments are passed to the horizontal, the bipolar, the amacrine, and the ganglion cells. (d) The primary phototransduction signal is generated in the receptor protein rhodopsin shown schematically at a much reduced density. The rhodopsin containing membranes form disks with a thickness of ~20 nm, being ~15–20 nm apart from each other. The putatively magnetic-field-sensitive protein cryptochrome may be localized in a specifically oriented fashion between the disks of the outer segment of the photoreceptor cell, as schematically shown in panel d or the cryptochromes (e) may be attached to the oriented, quasicylindrical membrane of the inner segment of the photoreceptor cell (f).

A third example of quantum trickery in biology – is the mechanism by which birds and other animals make use of the Earth’s magnetic field for navigation. Studies of the European robin suggest that it has an internal chemical compass that utilises an astonishing quantum concept called entanglement, which Einstein dismissed as “spooky action at a distance”. This phenomenon describes how two separated particles can remain instantaneously connected via a weird quantum link. The current best guess is that this takes place inside a protein in the bird’s eye, where quantum entanglement makes a pair of electrons highly sensitive to the angle of orientation of the Earth’s magnetic field, allowing the bird to “see” which way it needs to fly.

The avian magnetic sensor is known to be activated by light striking the bird’s retina. Researchers’ current best guess at a mechanism is that the energy deposited by each incoming photon creates a pair of free radicals. [Ritz, T., Thalau, P., Phillips, J. B., Wiltschko, R. & Wiltschko, W. Nature 429, 177–180 (2004).] — highly reactive molecules, each with an unpaired electron. Each of these unpaired electrons has an intrinsic angular momentum, or spin, that can be reoriented by a magnetic field. As the radicals separate, the unpaired electron on one is primarily influenced by the magnetism of a nearby atomic nucleus, whereas the unpaired electron on the other is further away from the nucleus, and feels only Earth’s magnetic field. The difference in the fields shifts the radical pair between two quantum states with differing chemical reactivity.

Radical Pair

Panoramic view at Frankfurt am Main, Germany. The image shows the landscape perspective recorded from a bird flight altitude of 200 m above the ground with the cardinal directions indicated. The visual field of a bird is modified through the magnetic filter function. For the sake of illustration we show the magnetic field-mediated pattern in grayscale alone (which would reflect the perceived pattern if the magnetic visual pathway is completely separated from the normal visual pathway) and added onto the normal visual image the bird would see, if magnetic and normal vision uses the same neuronal pathway in the retina. The patterns are shown for a bird looking at eight cardinal directions (N, NE, E, SE, S, SW, W, and NW). The geomagnetic field inclination angle is 66°, being a characteristic value for the region.

“One version of the idea would be that some chemical is synthesized in the bird’s retinal cells when the system is in one state, but not when it’s in the other”, says Simon Benjamin, a physicist at the University of Oxford, UK. “Its concentration reflects Earth’s field orientation.” The feasibility of this idea was demonstrated in 2008 in an artificial photochemical reaction, in which magnetic fields affected the lifetime of a radical pair.[Maeda, K. et al. Nature 453, 387–390 (2008).]

The radical-pair mechanism for avian magnetoreception explains many of the behavioural studies performed on some species of migrating birds. Key properties of the proposed radical-pair model for avian magnetoreception are dependent on quantum mechanics; therefore, this may represent a functional piece of biological quantum hardware. a, A schematic of the radical-pair mechanism for magnetoreception that could potentially be employed by European robins and other species. It is thought to occur within cryptochromes, proteins residing in the retina. There are three main steps in this mechanism. First, light-induced electron transfer from one radical-pair-forming molecule (for example, in a cryptochrome in the retina of a bird) to an acceptor molecule creates a radical pair. b,c, Second, the singlet (S) and triplet (T) electron-spin states inter-convert owing to the external (Zeeman) and internal (hyperfine) magnetic couplings. d, Third, singlet and triplet radical pairs recombine into singlet and triplet products, respectively, which are biologically detectable. e, Singlet yield (a measure of the probability of the radical pair to decay into a singlet state) as a function of the external-field angle θ in the presence of an oscillatory field (taken from Gauger et al. 70). The blue top curve shows the yield for a static geomagnetic field (B0 = 47 μT), and the red curves show the singlet yield in the case where a 150 nT field oscillating at 1.316 MHz is superimposed perpendicular to the direction of the static field. The sensitivity of the compass can be understood as the difference in the yield between θ = 0 and θ = π/2. An appreciable effect on this sensitivity occurs once κ (the decay rate of the radical) is of order 104 s−1. f, Singlet yield as a function of the magnetic field angle θ for differing noise magnitudes (from Gauger et al. 70). The blue curve shows the optimal case with no noise (but with decay rate κ = 104 s−1). The red curves indicate that a general noise rate of Γ>0.1κ has a detrimental effect on the sensitivity. Both of these results indicate that the electron spin state must have a remarkably long coherence time.

Benjamin and his co-workers have proposed that the two unpaired electrons, being created by the absorption of a single photon, exist in a state of quantum entanglement: a form of coherence in which the orientation of one spin remains correlated with that of the other, no matter how far apart the radicals move. Entanglement is usually quite delicate at ambient temperatures, but the researchers calculate that it is maintained in the avian compass for at least tens of microseconds — much longer than is currently possible in any artificial molecular system. [Gauger, E. M., Rieper, E., Morton, J. J. L., Benjamin, S. C. & Vedral, V. Phys. Rev. Lett. 106, 040503 (2011).]

Reference: The Dawn of Quantum Biology by Philip Ball , Nature, Vol. 474, 16 June 2011, pg 272-274.

This quantum-assisted magnetic sensing could be widespread. Not only birds, but also some insects and even plants show physiological responses to magnetic fields — for example, the growth-inhibiting influence of blue light on the flowering plant Arabidopsis thaliana is moderated by magnetic fields in a way that may also use the radical pair mechanism. [Ahmad, M., Galland, P., Ritz, T., Wiltschko, R. & Wiltschko, W. Planta 225, 615–624 (2007)] But for clinching proof that it works this way, says Benjamin, “we need to understand the basic molecules involved, and then study them in the lab”.

All these quantum effects have come as a big surprise to most scientists who believed that the quantum laws only applied in the microscopic world. All delicate quantum behaviour was thought to be washed away very quickly in bigger objects, such as living cells, containing the turbulent motion of trillions of randomly moving particles. So how does life manage its quantum trickery? Recent research suggests that rather than avoiding molecular storms, life embraces them, rather like the captain of a ship who harnesses turbulent gusts and squalls to maintain his ship upright and on course.

Just as Schrödinger predicted, life seems to be balanced on the boundary between the sensible everyday world of the large and the weird and wonderful quantum world, a discovery that is opening up an exciting new field of 21st-century science.

Reference: You’re powered by quantum mechanics. No, really…