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Scientific Life
Engineering
‘Posthumans’: To Be
or Not to Be?
Marianna Karamanou,1
Theodore G. Papaioannou,2,
*
Dimitrios Soulis,2
and
Dimitrios Tousoulis2
Emerging technological innova-
tions have transformed some sci-
ence fiction ideas into reality,
promising radical changes in
human nature. New philosophical
and intellectual movements such
as ‘transhumanism’ and ‘posthu-
manism’ try to foretell and even
direct the future of our existence
while dealing with new and com-
plex ethical, social, political issues
and dilemmas.
Technology and Human Evolution
Since antiquity, humans have sought to
invent technologies that enhance or
extend their ability to survive, adjust to
environmental conditions, outperform,
and achieve goals. From the ancient The-
riac, an all-purpose cure for a wide range
of illnesses [1], to modern medical tech-
nologies, the purpose remains the same:
treat or eradicate diseases, improve qual-
ity of living, and prolong the human life
span.
Over the last two decades, emerging
technological innovations in the fields of
biotechnology, information technology,
material science, electronics, nanotech-
nology, and robotics have transformed
some ideas from science fiction into real-
ity. Currently, bioengineered tissues and
artificial organs [2], brain–computer or
brain–machine interaction [3], and gene
editing [4] promise drastic changes in the
human species, while in the near future,
human functions, capacities, and even
fundamental rights will be transmuted into
a radically revised concept of what we
currently know as a ‘human being’.
Philosophical and Intellectual
Perspectives
As a precursor of this new world order,
philosophical theories and intellectual
movements have been born trying to fore-
tell and even direct the future of our exis-
tence while dealing at the same time with
new and complex ethical issues and
dilemmas. Since the huge production of
innovative medical technologies and ser-
vices are often accompanied by
increased costs, bioethical debates seem
to shift from rationing to the avoidance of
waste [5], triggering new social and politi-
cal trends. Two new philosophical and
intellectual movements, ‘transhumanism’
and ‘posthumanism’, may influence
future health policies. Interestingly, these
philosophical theories have already tran-
scended into political and religion move-
ments such as the ‘Transhumanist Party’,
an American political organization, dedi-
cated to putting science, health, and
technology in the forefront of United
States politics (http://www.
transhumanistparty.org), and the ‘Chris-
tian Transhumanist Association’, whose
purpose is described as ‘participating
with God in the redemption, reconcilia-
tion, and renewal of the world’ (http://
www.christiantranshumanism.org).
The term ‘transhumanism’ is historically
associated with the British evolutionary
biologist and philosopher Sir Julian Hux-
ley (1887–1975). In his book New Bottles
for New Wine he stated, ‘The human spe-
cies can, if it wishes, transcend itself . . .
man will remain man, but transcending
himself, by realizing new possibilities of
and for his human nature. I believe in
transhumanism: once there are enough
people who can truly say that, the human
species will be on the threshold of a new
kind of existence, as different from ours as
ours is from that of Peking man. It will at
last be consciously fulfilling its real des-
tiny’ [6]. Transhumanism evolves technol-
ogies that may overcome fundamental
human biological functions boosting
physical, intellectual, and psychological
capabilities and transforming humans to
a different entity defined as ‘transhuman’.
However, transhumanism focuses on
technologies that can enhance normal
human functions rather than create new
ones.
By contrast, posthumanism moves
beyond transhumanism and adopts ‘sci-
ence fiction’ ideas and concepts, accord-
ing to which the ‘posthuman’ will be the
biotechnologically mutated non-human, a
creature which will remain biologically
encased but at the same time separated
from its natural biological origin [7]. Others
describe the posthuman as the techno-
logical successor to the biological human,
namely a cyborg entity, inhabiting data
space and enjoying a computationally
generated consciousness unconstrained
by the physics of materiality and the pres-
sures of mortality (http://ieet.org). Post-
humanism focuses more on the function
of ‘beings’ rather than their appearance.
According to this school of thinking,
humans and machines will be effectively
merged.
Scientific and Social Awareness
on Transhumanism/
Posthumanism
Nevertheless, how much the scientific
community and the public are aware of
these philosophies? The scientific com-
munity (especially biomedical/biological
researchers) publishing their work in jour-
nals indexed by MEDLINE do not discuss
or write frequently about transhumanism/
posthumanism, as indicated by the
extremely small number of papers
(<100) published from 2003 until today
that include these terms. By contrast,
scientists who published their papers in
journals indexed by Scopus (which covers
a broader scientific field including philos-
ophy, history, theology, ethics, etc.) are
more frequently concerned about these
theories but still in a limited extent (up to
1000 publications so far). Notably, the
number of publications discussing
Trends in Biotechnology, August 2017, Vol. 35, No. 8 677
transhumanism and posthumanism has
increased during the last five years.
Social networks such as Twitter may pro-
vide information about public awareness
or interest on specific topics by mining
and analyzing data from posts that
include key terms of interest. Twitter is
a social media and microblogging site that
has rapidly grown in popularity, with more
than 320 million monthly active users who
generate more than 340 million tweets
daily; it also offers a great opportunity
for public health campaigns [8]. Using a
custom-made data mining computational
tool, we sought to find out how often
Twitter users discuss about these terms
(‘transhumanism’ OR ‘trans-humanism’
OR ‘posthumanism’ OR ‘post-human-
ism’). During a randomly selected period
of 1 month (May 2016) Twitter users men-
tioned these keywords in their posts 6179
times; which at a first glance seems to be
non-negligible.
Concluding Viewpoints
Decades ago, several ‘science fiction’
writers described imaginary technologies
some of which became reality, proving
the writers to be either prophets or
inspired scientists. One example is the
Luke Skywalker’s artificial arm in the Star
Wars film The Empire Strikes Back, which
inspired the ‘LUKE’ (Life Under Kinetic
Evolution), the successor of a Food and
Drug Administration-approved, DEKA
neuro-controlled arm. ‘LUKE’ can trans-
late electrical signals from electromyo-
gram electrodes, enabling users to
perform complex actions. Many more
examples exist, and more are to come.
Another similar case of science fiction that
turned into reality is the development and
use of ‘exoskeletons’. Several writers and
movies makers have described construc-
tions that can be used as wearable tech-
nologies to empower the functions of the
human body and provide supernatural
abilities transforming humans into super-
heroes. A powerful ‘body’ with mechani-
cal muscles appeared in science fiction in
middle 1860s in the dime novel The
Steam Man of the Prairies by Edward
Sylvester Ellis (1840–1916). The book
depicted a giant humanoid-shaped
steam engine invented by the ingenious
Johnny Brainerd, moving at speeds of 60
mi/h (96.5 km/h) chasing buffaloes and
terrorized Indians (Figure 1A). The ‘Iron-
Man’, appearing in the early 1960s in
Marvel Comics, is another classic exam-
ple. Today several types of exoskeletons
have been developed for medical, mili-
tary, or labor-working purposes
(Figure 1B,C).
Control of the human mind or technologi-
cal interfering with human memory or
thinking has been a main theme for sev-
eral science fiction movies. Mind control is
commonly perceived as ‘conspiracy the-
ory’ or ‘X-Files’ fare, and there is general
belief that brain code and function is still
an unexplored and very complex domain.
However, evidence-based scientific stud-
ies have shown that several sophisticated
mind control methods and technologies
are already under experimental develop-
ment, such as for memory modification
[9], genetically targeted magnetic control
of the nervous system [10], or brain-to-
brain communication [11].
One important challenge is the future of
human species from physical, cognitive,
and moral perspectives. Are we really
ready to ‘engineer’ humanity’s future and
manage the benefits and dangers derived
from the use of these emerging technolo-
gies in our life? Yes, under certain condi-
tions. Since antiquity, humans have been
trying to improve their life and health. Pre-
historic humans used animal skin to stay
warm; in antiquity, Hippocrates (460–377
BCE) provided science with a rational and
systemic basis that contributed to the con-
cept of methodology; medieval physicians
were trying through alchemy to find the
elixir of eternal health and longevity; and
the advent of chemistry, biochemistry, and
pharmacology at the end of 19th/begin-
ning of 20th century saved millions of lives
from plagues such as syphilis and tuber-
culosis. Currently, we use technology for
procreation (in vitro fertilization), transcath-
eter implantation of bioprosthetic aortic
valves as an alternative to open-heart sur-
gery,andtargetednanoparticlesforcancer
theranostics.
Therefore, ‘transhumanization’ toward an
advanced or/and artificially enhanced bio-
logical status is not really a new phenom-
enon or concept. Throughout history we
(A) (B) (C)
Figure 1. Exoskeletons in Science Fiction and Reality. (A) Cover of The Steam Man of the Prairies by
Edward S. Ellis (1882 edition). (B) Design of XOS exoskeleton developed by Sarcos Lab, capable of lifting over
200 lb, funded by the Defense Advanced Research Projects Agency (DARPA, USA; Source: https://
singularityhub.com). (C) HAL for Medical Use is a medical device (exoskeleton) for people who have disorders
in the lower limb and people whose legs are weakening.
678 Trends in Biotechnology, August 2017, Vol. 35, No. 8
were always in a state of perpetual
change and self-overcoming. It depends
on us to use any new technology for our
benefit, establishing and adopting rules
and behaviors under ethical and moral
terms. In this way, it will not be ‘appallingly
obvious that our technology has
exceeded our humanity’ as it was through
the eyes of Albert Einstein (1879–1955).
1
Institute of History of Medicine and Public Health,
Medical School, University of Lausanne, Lausanne,
Switzerland
2
Biomedical Engineering Unit, First Department of
Cardiology, Hippokration Hospital, Medical School,
National and Kapodistrian University of Athens, Athens,
Greece
*Correspondence: thepap@med.uoa.gr (.G. Papaioannou).
http://dx.doi.org/10.1016/j.tibtech.2017.04.011
References
1. Karaberopoulos, D. et al. (2012) The theriac in antiquity.
Lancet 379, 1942–1943
2. Marx, V. (2015) Tissue engineering: organs from the lab.
Nature 522, 373–377
3. Aflalo, T. et al. (2015) Neurophysiology. Decoding motor
imagery from the posterior parietal cortex of a tetraplegic
human. Science 348, 906–910
4. Travis, J. (2015) Making the cut. Science 350, 1456–1457
5. Brody, H. (2012) From an ethics of rationing to an ethics of
waste avoidance. N. Engl. J. Med. 366, 1949–1951
6. Huxley, J. (1957) New Bottles for New Wine, Chatto &
Windus
7. Pepperell, R. (2005) Posthumans and extended experi-
ence. J. Evol. Technol. 14, 27–41
8. Wehner, M.R. et al. (2014) Twitter: an opportunity for public
health campaigns. Lancet 384, 131–132
9. Nabavi, S. et al. (2014) Engineering a memory with LTD
and LTP. Nature 511, 348–352
10. Wheeler, M.A. et al. (2016) Genetically targeted magnetic
control of the nervous system. Nat. Neurosci. 19, 756–761
11. Min, B.K. and Muller, K.R. (2014) Electroencephalography/
sonication-mediated human brain-brain interfacing tech-
nology. Trends Biotechnol. 32, 345–346
Science & Society
Designer Probiotics:
Paving the Way to
Living Therapeutics
Birbal Singh,1,
* Gorakh Mal,1
and Francesco Marotta2
Enhancing the functional reper-
toire of probiotics is a promising
approach to cope with the
inexorable rise of antibiotic-resis-
tant pathogens and the rather slow
development of new antibiotics.
Probiotics that deliver novel thera-
peutics efficiently and with site
specificity are emerging living
therapeutics that may transform
existing paradigms of disease
diagnosis and prevention.
The normal microbiota are essential
determinants of vital processes such as
hematopoiesis, aging, immunity against
infectious diseases, and behavior.
Whereas the normal microbiota occa-
sionally fails to protect the host against
pathogens, a perturbed gut microbiota is
associated with inflammation, obesity,
insulin resistance, diabetes, cardiovascu-
lar diseases (CVDs), and neuropsychiatric
disorders.
The WHO has recently released a list of 12
antibiotic-resistant families of pathogenic
bacteria, described as ‘priority patho-
gens’, which pose a grave threat. Para-
doxically, the development of new
antibiotics has also slowed down, which
increases the demand for alternative ther-
apeutics. Expanding the efficacy of pro-
biotics by introducing new genetic circuits
to deliver drug biomolecules is crucial.
These recombinant probiotics, informally
called ‘designer probiotics’ or ‘probiotics
2.0’, are poised to reduce the gap
between the mounting antibiotic resis-
tance and the dearth of new antibiotics
[1–4].
The science of probiotics, which was for-
merly confined to basic microbiology and
food processing, has emerged in the
postgenomic era of medicine and biology
as a premier area of research towards
functional nutraceuticals, gastroenterol-
ogy, allergology, skin care, oncotherapy,
psychoneuroendocrinology, and veteri-
nary applications. The lactic acid bacteria
(LAB), bifidobacteria, Escherichia coli Nis-
sle 1917, and yeasts (Saccharomyces
cerevisiae, Saccharomyces boulardii,
Kluyveromyces lactis, and Pichia pastoris)
are some of the prospective probiotics
used for expressing heterologous genes
encoding antimicrobial and anti-inflam-
matory biomolecules.
Designer Probiotics against
Infectious Diseases
As the efficacy of orally administered anti-
gens is reduced during passage through
the alimentary tract, probiotic-mediated
drug delivery could be a promising strat-
egy for administering multiple therapeu-
tics (cytokines, antibody fragments,
antigens, peptides, etc.) in situ at the site
of infection, therefore circumventing the
side effects associated with the systemic
administration of drugs.
For example, the vaccination of mice with
recombinant Lactobacillus gasseri
NM713 expressing streptococcal M6
protein (CRR6) protected them against
streptococcus group A infections [5],
and recombinant Lactococcus lactis
(LL-Thy 12) expressing human interleu-
kin-10 (IL-10) provided relief from Crohn’s
disease (CD) [1]. Furthermore, L. lactis
strains that produce native (and pilin-
deleted) immunomodulatory surface pili-
ation appendages (SpaCBA) were found
to activate Toll-like receptor 2-dependent
signaling in cell lines and to modulate
synthesis of anti-inflammatory cytokines
(TNF-a, IL-6, IL-10, and IL-12) in human
dendritic cells [6]. Another study reported
recombinant L. lactis delivering therapeu-
tic proteins at mucosal surfaces in murine
models of human inflammatory bowel dis-
eases (IBDs) and human papillomavirus
type 16 (HPV-16) [7].
In addition, epidemiological, experimen-
tal, and clinical evidence convincingly
shows that genitourinary microbiota dom-
inated by LAB protect the host against
bacterial vaginosis (BV) and sexually
transmitted viral infections [9]. One con-
tributor to host protection is a group of
antimicrobial proteins including riboso-
mally-synthesized bacteriocins, micro-
cins, peptides, and the type VI secretion
Trends in Biotechnology, August 2017, Vol. 35, No. 8 679

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Engineering ‘Posthumans’: To Be or Not to Be?

  • 1. Scientific Life Engineering ‘Posthumans’: To Be or Not to Be? Marianna Karamanou,1 Theodore G. Papaioannou,2, * Dimitrios Soulis,2 and Dimitrios Tousoulis2 Emerging technological innova- tions have transformed some sci- ence fiction ideas into reality, promising radical changes in human nature. New philosophical and intellectual movements such as ‘transhumanism’ and ‘posthu- manism’ try to foretell and even direct the future of our existence while dealing with new and com- plex ethical, social, political issues and dilemmas. Technology and Human Evolution Since antiquity, humans have sought to invent technologies that enhance or extend their ability to survive, adjust to environmental conditions, outperform, and achieve goals. From the ancient The- riac, an all-purpose cure for a wide range of illnesses [1], to modern medical tech- nologies, the purpose remains the same: treat or eradicate diseases, improve qual- ity of living, and prolong the human life span. Over the last two decades, emerging technological innovations in the fields of biotechnology, information technology, material science, electronics, nanotech- nology, and robotics have transformed some ideas from science fiction into real- ity. Currently, bioengineered tissues and artificial organs [2], brain–computer or brain–machine interaction [3], and gene editing [4] promise drastic changes in the human species, while in the near future, human functions, capacities, and even fundamental rights will be transmuted into a radically revised concept of what we currently know as a ‘human being’. Philosophical and Intellectual Perspectives As a precursor of this new world order, philosophical theories and intellectual movements have been born trying to fore- tell and even direct the future of our exis- tence while dealing at the same time with new and complex ethical issues and dilemmas. Since the huge production of innovative medical technologies and ser- vices are often accompanied by increased costs, bioethical debates seem to shift from rationing to the avoidance of waste [5], triggering new social and politi- cal trends. Two new philosophical and intellectual movements, ‘transhumanism’ and ‘posthumanism’, may influence future health policies. Interestingly, these philosophical theories have already tran- scended into political and religion move- ments such as the ‘Transhumanist Party’, an American political organization, dedi- cated to putting science, health, and technology in the forefront of United States politics (http://www. transhumanistparty.org), and the ‘Chris- tian Transhumanist Association’, whose purpose is described as ‘participating with God in the redemption, reconcilia- tion, and renewal of the world’ (http:// www.christiantranshumanism.org). The term ‘transhumanism’ is historically associated with the British evolutionary biologist and philosopher Sir Julian Hux- ley (1887–1975). In his book New Bottles for New Wine he stated, ‘The human spe- cies can, if it wishes, transcend itself . . . man will remain man, but transcending himself, by realizing new possibilities of and for his human nature. I believe in transhumanism: once there are enough people who can truly say that, the human species will be on the threshold of a new kind of existence, as different from ours as ours is from that of Peking man. It will at last be consciously fulfilling its real des- tiny’ [6]. Transhumanism evolves technol- ogies that may overcome fundamental human biological functions boosting physical, intellectual, and psychological capabilities and transforming humans to a different entity defined as ‘transhuman’. However, transhumanism focuses on technologies that can enhance normal human functions rather than create new ones. By contrast, posthumanism moves beyond transhumanism and adopts ‘sci- ence fiction’ ideas and concepts, accord- ing to which the ‘posthuman’ will be the biotechnologically mutated non-human, a creature which will remain biologically encased but at the same time separated from its natural biological origin [7]. Others describe the posthuman as the techno- logical successor to the biological human, namely a cyborg entity, inhabiting data space and enjoying a computationally generated consciousness unconstrained by the physics of materiality and the pres- sures of mortality (http://ieet.org). Post- humanism focuses more on the function of ‘beings’ rather than their appearance. According to this school of thinking, humans and machines will be effectively merged. Scientific and Social Awareness on Transhumanism/ Posthumanism Nevertheless, how much the scientific community and the public are aware of these philosophies? The scientific com- munity (especially biomedical/biological researchers) publishing their work in jour- nals indexed by MEDLINE do not discuss or write frequently about transhumanism/ posthumanism, as indicated by the extremely small number of papers (<100) published from 2003 until today that include these terms. By contrast, scientists who published their papers in journals indexed by Scopus (which covers a broader scientific field including philos- ophy, history, theology, ethics, etc.) are more frequently concerned about these theories but still in a limited extent (up to 1000 publications so far). Notably, the number of publications discussing Trends in Biotechnology, August 2017, Vol. 35, No. 8 677
  • 2. transhumanism and posthumanism has increased during the last five years. Social networks such as Twitter may pro- vide information about public awareness or interest on specific topics by mining and analyzing data from posts that include key terms of interest. Twitter is a social media and microblogging site that has rapidly grown in popularity, with more than 320 million monthly active users who generate more than 340 million tweets daily; it also offers a great opportunity for public health campaigns [8]. Using a custom-made data mining computational tool, we sought to find out how often Twitter users discuss about these terms (‘transhumanism’ OR ‘trans-humanism’ OR ‘posthumanism’ OR ‘post-human- ism’). During a randomly selected period of 1 month (May 2016) Twitter users men- tioned these keywords in their posts 6179 times; which at a first glance seems to be non-negligible. Concluding Viewpoints Decades ago, several ‘science fiction’ writers described imaginary technologies some of which became reality, proving the writers to be either prophets or inspired scientists. One example is the Luke Skywalker’s artificial arm in the Star Wars film The Empire Strikes Back, which inspired the ‘LUKE’ (Life Under Kinetic Evolution), the successor of a Food and Drug Administration-approved, DEKA neuro-controlled arm. ‘LUKE’ can trans- late electrical signals from electromyo- gram electrodes, enabling users to perform complex actions. Many more examples exist, and more are to come. Another similar case of science fiction that turned into reality is the development and use of ‘exoskeletons’. Several writers and movies makers have described construc- tions that can be used as wearable tech- nologies to empower the functions of the human body and provide supernatural abilities transforming humans into super- heroes. A powerful ‘body’ with mechani- cal muscles appeared in science fiction in middle 1860s in the dime novel The Steam Man of the Prairies by Edward Sylvester Ellis (1840–1916). The book depicted a giant humanoid-shaped steam engine invented by the ingenious Johnny Brainerd, moving at speeds of 60 mi/h (96.5 km/h) chasing buffaloes and terrorized Indians (Figure 1A). The ‘Iron- Man’, appearing in the early 1960s in Marvel Comics, is another classic exam- ple. Today several types of exoskeletons have been developed for medical, mili- tary, or labor-working purposes (Figure 1B,C). Control of the human mind or technologi- cal interfering with human memory or thinking has been a main theme for sev- eral science fiction movies. Mind control is commonly perceived as ‘conspiracy the- ory’ or ‘X-Files’ fare, and there is general belief that brain code and function is still an unexplored and very complex domain. However, evidence-based scientific stud- ies have shown that several sophisticated mind control methods and technologies are already under experimental develop- ment, such as for memory modification [9], genetically targeted magnetic control of the nervous system [10], or brain-to- brain communication [11]. One important challenge is the future of human species from physical, cognitive, and moral perspectives. Are we really ready to ‘engineer’ humanity’s future and manage the benefits and dangers derived from the use of these emerging technolo- gies in our life? Yes, under certain condi- tions. Since antiquity, humans have been trying to improve their life and health. Pre- historic humans used animal skin to stay warm; in antiquity, Hippocrates (460–377 BCE) provided science with a rational and systemic basis that contributed to the con- cept of methodology; medieval physicians were trying through alchemy to find the elixir of eternal health and longevity; and the advent of chemistry, biochemistry, and pharmacology at the end of 19th/begin- ning of 20th century saved millions of lives from plagues such as syphilis and tuber- culosis. Currently, we use technology for procreation (in vitro fertilization), transcath- eter implantation of bioprosthetic aortic valves as an alternative to open-heart sur- gery,andtargetednanoparticlesforcancer theranostics. Therefore, ‘transhumanization’ toward an advanced or/and artificially enhanced bio- logical status is not really a new phenom- enon or concept. Throughout history we (A) (B) (C) Figure 1. Exoskeletons in Science Fiction and Reality. (A) Cover of The Steam Man of the Prairies by Edward S. Ellis (1882 edition). (B) Design of XOS exoskeleton developed by Sarcos Lab, capable of lifting over 200 lb, funded by the Defense Advanced Research Projects Agency (DARPA, USA; Source: https:// singularityhub.com). (C) HAL for Medical Use is a medical device (exoskeleton) for people who have disorders in the lower limb and people whose legs are weakening. 678 Trends in Biotechnology, August 2017, Vol. 35, No. 8
  • 3. were always in a state of perpetual change and self-overcoming. It depends on us to use any new technology for our benefit, establishing and adopting rules and behaviors under ethical and moral terms. In this way, it will not be ‘appallingly obvious that our technology has exceeded our humanity’ as it was through the eyes of Albert Einstein (1879–1955). 1 Institute of History of Medicine and Public Health, Medical School, University of Lausanne, Lausanne, Switzerland 2 Biomedical Engineering Unit, First Department of Cardiology, Hippokration Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece *Correspondence: thepap@med.uoa.gr (.G. Papaioannou). http://dx.doi.org/10.1016/j.tibtech.2017.04.011 References 1. Karaberopoulos, D. et al. (2012) The theriac in antiquity. Lancet 379, 1942–1943 2. Marx, V. (2015) Tissue engineering: organs from the lab. Nature 522, 373–377 3. Aflalo, T. et al. (2015) Neurophysiology. Decoding motor imagery from the posterior parietal cortex of a tetraplegic human. Science 348, 906–910 4. Travis, J. (2015) Making the cut. Science 350, 1456–1457 5. Brody, H. (2012) From an ethics of rationing to an ethics of waste avoidance. N. Engl. J. Med. 366, 1949–1951 6. Huxley, J. (1957) New Bottles for New Wine, Chatto & Windus 7. Pepperell, R. (2005) Posthumans and extended experi- ence. J. Evol. Technol. 14, 27–41 8. Wehner, M.R. et al. (2014) Twitter: an opportunity for public health campaigns. Lancet 384, 131–132 9. Nabavi, S. et al. (2014) Engineering a memory with LTD and LTP. Nature 511, 348–352 10. Wheeler, M.A. et al. (2016) Genetically targeted magnetic control of the nervous system. Nat. Neurosci. 19, 756–761 11. Min, B.K. and Muller, K.R. (2014) Electroencephalography/ sonication-mediated human brain-brain interfacing tech- nology. Trends Biotechnol. 32, 345–346 Science & Society Designer Probiotics: Paving the Way to Living Therapeutics Birbal Singh,1, * Gorakh Mal,1 and Francesco Marotta2 Enhancing the functional reper- toire of probiotics is a promising approach to cope with the inexorable rise of antibiotic-resis- tant pathogens and the rather slow development of new antibiotics. Probiotics that deliver novel thera- peutics efficiently and with site specificity are emerging living therapeutics that may transform existing paradigms of disease diagnosis and prevention. The normal microbiota are essential determinants of vital processes such as hematopoiesis, aging, immunity against infectious diseases, and behavior. Whereas the normal microbiota occa- sionally fails to protect the host against pathogens, a perturbed gut microbiota is associated with inflammation, obesity, insulin resistance, diabetes, cardiovascu- lar diseases (CVDs), and neuropsychiatric disorders. The WHO has recently released a list of 12 antibiotic-resistant families of pathogenic bacteria, described as ‘priority patho- gens’, which pose a grave threat. Para- doxically, the development of new antibiotics has also slowed down, which increases the demand for alternative ther- apeutics. Expanding the efficacy of pro- biotics by introducing new genetic circuits to deliver drug biomolecules is crucial. These recombinant probiotics, informally called ‘designer probiotics’ or ‘probiotics 2.0’, are poised to reduce the gap between the mounting antibiotic resis- tance and the dearth of new antibiotics [1–4]. The science of probiotics, which was for- merly confined to basic microbiology and food processing, has emerged in the postgenomic era of medicine and biology as a premier area of research towards functional nutraceuticals, gastroenterol- ogy, allergology, skin care, oncotherapy, psychoneuroendocrinology, and veteri- nary applications. The lactic acid bacteria (LAB), bifidobacteria, Escherichia coli Nis- sle 1917, and yeasts (Saccharomyces cerevisiae, Saccharomyces boulardii, Kluyveromyces lactis, and Pichia pastoris) are some of the prospective probiotics used for expressing heterologous genes encoding antimicrobial and anti-inflam- matory biomolecules. Designer Probiotics against Infectious Diseases As the efficacy of orally administered anti- gens is reduced during passage through the alimentary tract, probiotic-mediated drug delivery could be a promising strat- egy for administering multiple therapeu- tics (cytokines, antibody fragments, antigens, peptides, etc.) in situ at the site of infection, therefore circumventing the side effects associated with the systemic administration of drugs. For example, the vaccination of mice with recombinant Lactobacillus gasseri NM713 expressing streptococcal M6 protein (CRR6) protected them against streptococcus group A infections [5], and recombinant Lactococcus lactis (LL-Thy 12) expressing human interleu- kin-10 (IL-10) provided relief from Crohn’s disease (CD) [1]. Furthermore, L. lactis strains that produce native (and pilin- deleted) immunomodulatory surface pili- ation appendages (SpaCBA) were found to activate Toll-like receptor 2-dependent signaling in cell lines and to modulate synthesis of anti-inflammatory cytokines (TNF-a, IL-6, IL-10, and IL-12) in human dendritic cells [6]. Another study reported recombinant L. lactis delivering therapeu- tic proteins at mucosal surfaces in murine models of human inflammatory bowel dis- eases (IBDs) and human papillomavirus type 16 (HPV-16) [7]. In addition, epidemiological, experimen- tal, and clinical evidence convincingly shows that genitourinary microbiota dom- inated by LAB protect the host against bacterial vaginosis (BV) and sexually transmitted viral infections [9]. One con- tributor to host protection is a group of antimicrobial proteins including riboso- mally-synthesized bacteriocins, micro- cins, peptides, and the type VI secretion Trends in Biotechnology, August 2017, Vol. 35, No. 8 679