Can life forms exist from simple structures not made of the four bases?

Can life forms exist from simple structures not made of the four bases?

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I understand that all life forms on the planet are made from adenine, gauatine, cytosine and thymine, which chemically joined together to form RNA or DNA (correct me if I'm wrong). This goes on to form all complex life as we know it.

I was wondering if it was possible- even studied theoretically- that other life forms could exist made of different elements and compounds, perhaps let's say iron, cobalt or tungsten? Or are the 4 bases the only possible way of life as we currently know it?

So this question is difficult to answer because it has some errors in it, in that lifeforms being dependent on rarely used elements is a different question than lifeforms using different DNA bases, but I will answer both.

So for the question about whether or not organisms could exist that use DNA bases not found in organisms on earth, the answer is certainly yes.[1,2]

The above reference shows a very elegant example of completely synthetic DNA bases being incorporated into E Coli and propagated in culture without providing any noticeable negative effects. This provides strong support that life on Earth developed around the same 5 bases (CTGAU) by chance.

As for whether or not organisms could rely heavily on elements other than H,C,N,O, and P, this is certainly possible and evident already here on Earth. Extremophiles are a general class of organisms that have some pretty interesting properties to them. Some metabolize sulfur or metals, others live in really extreme temperatures or in areas of high radiation.

So really yes in both cases, life can really take numerous shapes and forms even when it seems completely impossible for them to do so.

Life's First Spark Re-Created in the Laboratory

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To revist this article, visit My Profile, then View saved stories.

A fundamental but elusive step in the early evolution of life on Earth has been replicated in a laboratory.

Researchers synthesized the basic ingredients of RNA, a molecule from which the simplest self-replicating structures are made. Until now, they couldn't explain how these ingredients might have formed.

"It's like molecular choreography, where the molecules choreograph their own behavior," said organic chemist John Sutherland of the University of Manchester, co-author of a study in Nature Wednesday.

RNA is now found in living cells, where it carries information between genes and protein-manufacturing cellular components. Scientists think RNA existed early in Earth's history, providing a necessary intermediate platform between pre-biotic chemicals and DNA, its double-stranded, more-stable descendant.

However, though researchers have been able to show how RNA's component molecules, called ribonucleotides, could assemble into RNA, their many attempts to synthesize these ribonucleotides have failed. No matter how they combined the ingredients — a sugar, a phosphate, and one of four different nitrogenous molecules, or nucleobases — ribonucleotides just wouldn't form.

Sutherland's team took a different approach in what Harvard molecular biologist Jack Szostak called a "synthetic tour de force" in an accompanying commentary in Nature.

"By changing the way we mix the ingredients together, we managed to make ribonucleotides," said Sutherland. "The chemistry works very effectively from simple precursors, and the conditions required are not distinct from what one might imagine took place on the early Earth."

Like other would-be nucleotide synthesizers, Sutherland's team included phosphate in their mix, but rather than adding it to sugars and nucleobases, they started with an array of even simpler molecules that were probably also in Earth's primordial ooze.

They mixed the molecules in water, heated the solution, then allowed it to evaporate, leaving behind a residue of hybrid, half-sugar, half-nucleobase molecules. To this residue they again added water, heated it, allowed it evaporate, and then irradiated it.

At each stage of the cycle, the resulting molecules were more complex. At the final stage, Sutherland's team added phosphate. "Remarkably, it transformed into the ribonucleotide!" said Sutherland.

According to Sutherland, these laboratory conditions resembled those of the life-originating "warm little pond" hypothesized by Charles Darwin if the pond "evaporated, got heated, and then it rained and the sun shone."

Such conditions are plausible, and Szostak imagined the ongoing cycle of evaporation, heating and condensation providing "a kind of organic snow which could accumulate as a reservoir of material ready for the next step in RNA synthesis."

Intriguingly, the precursor molecules used by Sutherland's team have been identified in interstellar dust clouds and on meteorites.

"Ribonucleotides are simply an expression of the fundamental principles of organic chemistry," said Sutherland. "They're doing it unwittingly. The instructions for them to do it are inherent in the structure of the precursor materials. And if they can self-assemble so easily, perhaps they shouldn't be viewed as complicated."

*Citations: Synthesis of activated pyrimidine ribonucleotides in prebiotically plausible conditions Matthew W. Powner, Beatrice Gerland & John D. Sutherland. Nature, Vol. 460, May 13, 2009.

*"Systems chemistry on early Earth." By Jack W. Szostak. **Nature, Vol. 460, May 13, 2009.

Biology Questions and Answers Form 4 - Biology Form Four Notes

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KCSE Revision Questions and Answers

Biology Form 4 Notes - Biology Form Four Notes

a) i) Define the term genetics

ii) List some characteristics which are inherited

iii)State the importance of genetics

b) i) Explain the meaning of the following terms

ii) List the types of chromosomes

c) i) What is variation?

ii) State the causes of variation in organisms

iii) Name the types of variation

iv) Explain the following terms

Acquired characteristics

Dominant gene (character)

d) i) Explain Mendels first law of inheritance

ii) Give an example of this law

iii) What is monohybrid inheritance?

i) What is complete dominance?

ii) Give an example of co dominance

In a certain plant species, some individual plants may have only white, red or pink flowers. In an experiment a plant with white flowers was crossed with a parent with red flowers. Show results of Fl generation. Use letter R for red gene and W for white gene.

If the plants form F1 were selfed, work out the phenotype ratio for the F2 generation Phenotypic ratio 1 red:2 pink: 1 white

f) i) What is a test cross?

ii) State the importance of a test cross in genetics

iii) What are multiple alleles?

example is blood group which can be determined by any two of three alleles i.e. A,B and O

iv) Explain the inheritance of ABO blood groups

ii) Explain the inheritance of Rhesus factor (Rh) in human beings

people who have Rh antigen are Rh(+ve) while those without Rh antigen in their blood are Rh(-ve)

recessive the result is as shown below

Let the gene for dominant Rh factor be R while gene for recessive be r

iii) How is sex determined in human beings .

g) i) What does the term linkage mean?

- These are genes which occur together on a chromosome and are passed to offspring without being separated ii) Define the term sex-linked genes

iii) What is meant by the term sex linkage?

iv) Name the sex-linked traits in humans

v) Give an example of a sex linked trait in humans on:

vi) In humans red-green colour blindness is caused by a recessive gene C, which is sex- linked. A normal man married to a carrier Woman transmits the trait to his children. Show the possible genotypes of the children.

Let C represent the gene for normal colour vision (dominant)

Let c represent the gene for colour blindness

Parental phenotype Norman man x carrier woman

iv) State the importance of sex linkage

possible to determine sex of day old chicks

v) Haemophilia is due to a recessive gene. The gene is sex-linked and located on the x chromosome. The figure below shows sworn offspring from phenotypically normal parents

What are the parental genotypes?

Work out the genotypes of the offspring

ii) Describe how mutations arise

iii)State the factors that may cause mutation

X-rays gene/chromosome alteration

Ultra violet rays structural distortion of DNA

colchicines prevents spindle formation

Cyclamate chromosome aberrations

Mustard gas chromosomes aberrations

Nitrous acid adenine in DNA is deaminated so behaves like guanine

Acridone orange addition and removal of bases of DNA

iv) State the characteristics of mutations

v) Explain chromosomal mutation

- Change in nature, structure or number of chromosomes

vi) Explain how the following types of chromosomal mutations occur

vii) What are gene mutations?

i) Explain how the following occur during gene mutation

I. State the practical applications of genetics

i. Breeding programmes (research)

ii. Genetic engineering

- legal questions of paternity knowledge of blood groups or blood transfusion

iv) Genetic counseling

Understanding human evolution and origin of other species.

2. a) i) Explain the meaning of evolution

ii) Differentiate organic evolution from chemical evolution as theories of origin of life

iii) What is special creation?

b) Discuss the various kinds of evidence for evolution

ii) Comparative anatomy

iii) Comparative embryology

iii) Comparative serology/physiology

iv) Geographical distribution

as a result of continental drift isolation of organisms occurred bring about different patterns of evolution

vi) Cell biology (cytology)

c) i) State the evolutionary characteristics that adopt human beings to the environment

- Upright posture/bipedal locomotion

ii) State the ways in which Homo sapiens differs from Homo habilis

d) i) Explain Larmarck’s theory of evolution

- Inheritance of acquired characteristics/environment induces production of a favorable trait which is then inherited

ii) Explain why Lamarck’s theory of evolution is not accepted by biologists today

- evidence does not support Lamarck’s theory

- acquired characteristics are not inherited/inherited characteristics are found in reproductive cells only

iii) Explain Darwin’s theory of evolution

- inheritance of genetically acquired characteristics

- a character happens to appear spontaneously which gives advantage to an organism therefore adapted then inherited through natural selection

e) i) What is natural selection?

- Organisms with certain characteristics are favoured by the environment

Such organisms tend to survive and produce viable offspring

Others not favored are eliminated from subsequent generations

ii) With examples, explain how natural selection takes place

- organism with certain characteristics are favored by their environment

- such organisms tend to survive and produce viable offspring

- others not favored are eliminated from subsequent generations

- as the environmental conditions change the survival value of a character may alter with time so that characteristics which were favored may no longer have advantage and other characters may then become favorable

- if a favorable character is inherited, then offspring produce generations which are better adapted to survive in a population

- more offspring are produced than can survive which results in struggle for survival - the fittest survive

iii) State the advantages of natural selection to organisms

- assist to eliminate disadvantageous characteristics/perpetuates advantageous characteristics

- allows better adapted organisms to survive adverse changes in the environment/less adapted organisms are eliminated

iv) State the ways in which sexual reproduction is important in the evolution of plants and animals

- brings about useful variations/desirable characters

- variations make offspring better adapted for survival/more resistant to diseases

- may lead to origin of new species

v) Explain the significance of mutation in evolution

- Mutation bring about variation which can be inherited

- Some of these variations are advantageous to the organism

- Others are disadvantageous

- The advantageous variations favour the organism to compete better in the struggle for survival

- This results into a more adapted organism to its environment or new species/varieties

- Those with disadvantageous characters will be discriminated against therefore eliminated from the population/death/perish

vi) Plain why it is only mutations in genes of gametes that influence evolution

- gametes form the new offspring

vii) How would you prove that evolution is still taking place?

- resistance of organism to antibiotics, pesticides and drugs

- new varieties of bacteria are resistant to certain antibiotics such as penicillin

- houseflies and mosquitoes are resistant to DDT

vii) Explain why some bacteria develop resistance to a drug after they have bee subjected to it for some time

- bacteria mutates/develops a new strain/chemical composition is altered hence is able to produce enzymes/chemicals which degrade the drug rendering it non-susceptible to the drug

- the new strain is favoured by selection pressure natural selection

f) How has industrial melaninism i.e. peppered moth contributed towards the mechanism of evolution

- This is an example of natural selection

- The peppered moth exists in two distinct forms, the speckled white form (normal form) and a melanic form (the black/dark)

- They usually rest on leaves and barks of trees that offer camouflage for protection

- Originally the “speckled white” form predominated the unpolluted area of England

- This colouration offered protection against predatory birds

- Due to industrial pollution tree barks have blackened with soot

- The white form underwent mutation

- A black variety/mutant emerged suddenly by mutation

- It had selective advantage over the white forms that were predated upon in the industrial areas

- The speckled white form is abundant in areas without soot/smoke

3. a) i) Define irritability, stimulus and response irritability

- Responsiveness to change in environment

A change in the environment of organism which causes change in organism’s activity

- change in activity of an organism caused by a stimulus

ii) State importance of irritability to living organisms

- Adjusting to environmental conditions. Sensitive/defect/responding

iii) List the examples of external stimuli to organisms

- chemical concentration (chemo)

b) i) What are tactic responses?

- response in which whole organism or its motile parts move e. g. gamete

ii) What causes tactic responses?

- caused by unidirectional stimulus

- usually doesn’t involve growth

- response is either positive or negative

- named according to source of stimulus

- e.g phototaxis, aerotaxis, chemotaxis

iii) State the importance of tactic response to:

Members of kingdom protista

- move towards favorable environment/move away from unfavorable environment

- move towards their prey/food

- escape injurious stimuli/seek favorable habitats

iv) Name the type of response exhibited by:

Euglena when they swim towards the source of light

- sperms when they swim towards the ovum

v) State the advantages of tactic responses to organisms

- to avoid unfavorable environment/injurious stimuli

- to seek favorable environment

c) i) Define the term tropism

- growth movement of plants in response to external unilateral/unidirectional stimuli

ii) Explain the various types of tropism in plants

- growth movements of plant shoots in response to unilateral sources of light

- the tip of the shoots produce auxins down the shoot

- light causes auxins to migrate to outer side/darker side causing growth on the side away from light hence growth curvature towards source of light roots are negatively phototrophic

- response of roots/pans of a plant to the direction of force of gravity

- auxins grow towards the direction of force of gravity causing positive geotropism in roots while shoot grows away from force of gravity (negatively geotrophic)


- growth response of plant when in contact with an object

- contact with support causes migration of auxins to outer side causing faster growth on the side away from contact surface

- this causes tendrils/stem to twin around a support

- growth movement of roots in response to unilateral source of water/moisture

- the root grows towards the source of water/ positively hydrotropic while leaves are negatively hydrotropic

- growth movement of parts of plant to unilateral source of chemicals

- the chemicals form a gradient between two regions e.g. pollen tube growing towards the ovary through the style

iii) State the ways in which tropisms are important to plants

- expose leaves/shoots in positions for maximum absorption of sunlight for photosynthesis

- enables roots of plants to seek/look/search for water

- enables plant stems/tendrils to obtain mechanical support especially those that lack woody stems.

- enables roots to grow deep into the soil for anchorage

- enables pollen tube grow to embryo sac to facilitate fertilization

iv) Explain the differences between tropic and tactic responses

-growth curvature in response

d) The diagram below represents growing seedlings which were subjected to unilateral light at the beginning of an experiment

i) State the results of P, Q and R after S days

- P will bend/grow towards light

- Q will remain straight/have little or no growth

- R will remain/grow straight/grow upwards

ii) Account for your results in (i) above

P- Growth substance/growth hormone/IAA/auxin are produced by the stem tip

- they move (downwards and get distributed) to the side away from light where they cause rapid/more growth/cell division/elongation that results in bending

Q- Source of auxin has been removed

R- The auxins cannot be affected by light because the tip has been covered

iii) If the tin foil were removed from the tip of seedling R, what results would be observed after two days

- it will bend/grow towards light

iv) State the expected results after 3 day is if the box were removed

- all seedlings will grow straight/upwards

e) In an experiment to investigate a certain aspect of plant response, a seedling was placed horizontally as shown in diagram I below. After seven days the appearance of the seedling was as shown in diagram 2

Account for the curvature of the shoot and root after the seven days

- auxins accumulate on the lower side of the seedling due to gravity

- high concentration of auxins in shoot stimulates faster growth causing more elongation on the lower side than the upper side hence curvature occurs upwards

- the high concentration of auxins inhibits growth hence the upper side with less auxins grows faster than the lower side therefore the curvature occurs downwards

- phenomenon exhibited by plants when grown in darkness

- such plants are pale yellow due to absence of chlorophyll, have small leaves, long stems/hypocotyle and slender stems

- plants exhibit etiolation to reach light/obtain light

- this is a survival response

4. a) i) What is coordination in animals

- The linking together of all physiological activities that occur in the body so that they take place at the night time and in the correct place

ii) Name the main systems for coordination in animals

- Nervous system/sensory system

- Endocrine (hormonal system)

iii) List the components of the mammalian sensory system

- Central nervous system (CNS), brain & spinal cord

- Peripheral nervous system (PNS) cranial and spinal nerves

- Autonomic nervous system (ANS) nerve fibers and ganglia

iv).Explain the terms receptors, conductors and effectors

- Receptors are structures that detect stimuli i.e. sense organs

- Conductors transmit impulses from receptors to effectors e. g. neurons

- Effectors are the responding parts e.g. muscles, glands

v) What are the functions of the central nervous system?

- provides a fast means of communication between receptors and effectors

- coordinates the activities of the body

vi) State the differences between somatic and autonomic systems of peripheral nervous system

- Somatic is concerned with controlling the conscious or voluntary actions of the body i.e. skin, bones, joints and skeletal muscles

- the autonomic (automatic) nervous system controls involuntary actions of internal organs, digestive system, blood vessels, cardiac muscles and glandular products.

b) i) What is a neurone?

ii) Name the parts of a typical neurone and state the functions of each part

i) Describe the structure and function of a motor neurone

ii) Describe the structure and of sensory neurone

iii) State structural differences between motor and sensory neurons

iv) Describe the structure and function of a relay neurone

c) State the function of the major parts of the human brain

a) i) What is reflex action?

ii) Describe a reflex action that will lead to the Withdrawal of a hand from a hot object

iii) Explain how an impulse is transmitted across the synapse (gap)

ii) Briefly describe the transmission of a nervous impulse across a neuro-muscular junction

iii) What are the functions of a synapse?

b) i) What is a conditioned reflex?

ii) Explain a conditioned reflex

iii) Compare a simple reflex action with a conditioned reflex

c) i) What are endocrine glands?

ii) State the functions of hormones in animals

iii) Name the main endocrine glands, their secretions and functions in the human body

increases the rate of metabolism

regulates calcium and phosphate levels

regulates growth of the body

gonadotrophic hormone

stimulates the growth of male and female organs

lactogenic hormone (prolactine)

stimulates secretion of milk after child birth

thyrotropic hormone( TSH)

proper functioning of thyroid glands/thyroxine production

adrenocorthicotropic hormone (ACTH)

stimulate release of adrenal cortex hormone

stimulates smooth muscles

stimulates contraction of uterus during child birth

aids flow of milk from mammary glands

follicle stimulating hormone (FSH)

causes maturition of egg in females

stimulates sperm production in male

Vasopressin (ADH) antidiuretic hormone

regulates water balance by kidney

adrenaline (epinephrine hormone)

prepares body to cope up with stress

maintain balance of salt and water in blood

break down the stored proteins to amino acids

aids in the break down of adipose tissue

regulates sugar levels in the blood

supplements sex hormones produced by gonads

promotes development of sexual characteristics

regulates levels of sugar in blood

enables liver to store sugars

regulates levels of sugar in blood

oestrogen Function:

causes secondary sexual characteristics in female

prepares the uterus for pregnancy

progesterone Function:

growth of mucus lining of uterus

androgen testosterone

causes secondary sexual characteristics in male

stimulates release of gastric juice

stimulates secretion of pancreatic juice

iv) Give the differences between nervous and endocrine (hormonal) communication

v) State the effects of over secretion and under secretion of adrenaline and thyroxine in humans

g) i) Define the following terms

ii) State the types of drugs, examples and side effects

iii) State the general effects of drug abuse on human health

h) i) List the special sense organs in mammals and the major function of each

- Ear for hearing and balance

- Skin for touch, temperature detection, pain detection

iii) How is the human eye adapted to its function?

iii) What is accommodation of the eye?

iv) Explain how an eye viewing a near object adjusts to viewing a far object

v) What changes occur in the eye if it changes from observing an object at a distance to one at a closer range?

- Tension in suspensory ligaments reduces/relaxes slackens

- Lens bulges/thickens/increases curvature

- Size of pupil becomes large to allow in more light.

viii) State the changes which would take place in the eye if a person in a dark room had lights switched on

ix) Explain how the eye forms an image

x) Name the defects of the eye and state how they can be corrected

Long sight (Hypermetropia)

near image is formed behind the retina but a distant one is correctly focused on the retina

xi) State the advantages of having two eyes in human beings

i) What are the functions of the human ear?

iv) How are the structures of the human ear suited to perform the function of hearing?

iii) Explain how the structure of the human ear performs the function of balancing

sensory impulses are generated

iv) State what would happen if the auditory nerve was completely damaged

5. a) i) What is support?

ii) What is locomotion?

iii) State the importance of support systems in living organisms

iv) State the importance of locomotion in animals

b) i) Name the tissues in higher plants that provide mechanical support

ii) State the importance of support in plants

iii) Name the types of plant stems

iv) Name the tissues in plants that are strengthened with lignin

v) What makes young herbaceous plants remain upright?

vi) State the ways by which plants compensate for lack of ability to move from one place to another

c) i) Explain the Ways in which erect posture is maintained in a Weak herbaceous stem

- This is the function of turgidity and presence of collencyma

Cells take in water and become turgid

ii) Explain how support in plants is achieved

d) i) Give the reasons why support is necessary in animals

ii) Why is movement necessary in animals?

e) i) Name the organ used for support by animals

ii) Name the different types of skeletons in animals, giving an example of an animal for each type of skeleton named

iii) State the difference between exoskeleton and endoskeleton

iv) State the advantages of having an exoskeleton

v) Explain the importance of having an endoskeleton

f) i) Explain how a fish is adapted to living in Water

ii) Explain how a finned fish is adapted, to locomotion in Water

g) i) Name the main parts of the vertebral column giving the types of bones found in each part

Appendicular skeleton

hind limbs are connected to the pelvic girdle (hips)

ii) What are the vertebrae?

iii) State the functions of the vertebral column

iv) State the general characteristics of vertebrae

v) Name the bones of the vertebral column

vi) Describe how the various vertebrae are adapted to their functions

cervical region Atlas (first cervical)

cervical (others) Structure:

vii) Describe the bones that form the appendicular skeleton

pectoral girdle (scapular shoulder bone)

ii) State the functions of joints

iii) Name the main types of joints

iv) Give the features of movable joints

b) Describe the synovial joints

c) i) What is synovial fluid?

ii) State the functions of synovial fluid

d) Explain the following terms

ii) State the functions of muscles

f) Describe the structure and function of various types of muscles

ii) Involuntary muscles

organs, bladder, uterus, urinary tract, reproductive system, respiratory tract, ciliary body iris

g) Explain how muscles cause movement of the human arm

h) i) State the structural differences between skeletal muscles e.g. biceps and smooth muscles e.g. gut muscle

ii) Name the cartilage found between the bones of the vertebral column

iv) What are the functions of the cartilage named in (d) ii) above

The Properties of Water

Water (H2O) is fundamental to the existence of life as we know it. Indeed, it is so familiar to us that we take its properties for granted. What makes water so important? Why does water exist? What is the relationship between water and other biomolecules? In order to answer these questions we need to take a close look at water and at some of the subatomic properties of its electrons, which have a profound influence on its character.

As you probably learned in elementary school, a single molecule of water consists of two hydrogen atoms covalently bound to one oxygen atom. This arrangement does not sound very exciting, however, a closer examination of the bonds within the water molecule reveals something unique. Specifically, water is a polar molecule, meaning that it has different electrical properties on opposite ends specifically, it has two partial positive charges in association with the two H-atoms, and two partial negative charges associated with the oxygen atom.

Figure 1. Hydrogen bonds between water molecules. (Click to enlarge)

To understand these electrical properties, you need to know that not all covalent bonds (those bonds that involve the sharing of electrons) are equal. Specifically, oxygen tends to pull electrons close to itself when forming covalent bonds with hydrogen. This creates an unequal distribution around each O-H bond therefore, the hydrogen has a partial positive charge (and conversely, the oxygen has a slightly negative character). Importantly, the partial negative charges on one water molecule can interact with the partial positive charges on another water molecule to form a hydrogen bond (as shown in Figure 1 with dotted lines). Hydrogen bonds contribute to many of the unique features of water.

Synthetic Biology: Origin, Scope, and Ethics

Get weekly dispatches with the latest ideas from our thinking community.

And yet synthetic biology&mdashunlike chemistry&mdashis involved in the technical alteration of animate nature. Building on recent advances in genetic science and technology, synthetic biology aims to understand the molecular fundamentals of the metabolic and reproductive functions of simple single-cell organisms precisely. It thereby seeks to enable us thoroughly to manipulate and rearrange existing organisms in a standardised manner, and to equip them with characteristics that do not occur in nature.

It is hardly surprising that this technology provokes heated response. Colloquially, the term &ldquolife&rdquo (even when it is artificially constructed), is not merely a descriptive but invariably also a normative concept. Vitality&mdashbeing alive&mdashis the nucleus of that which, with wider cultural reference, implies worthiness of protection, at the very latest when living things display evidence of pain perception and simple forms of awareness moreover, vitality frequently means unpredictability and individualism. Finally, we often associate vitality with some sense of an inherent right to exist.

The creation of life in the laboratory counts as one of the literary and culturally pivotal codes for the goals of modern humanity, both in the form of the ideal and the &ldquowriting on the wall.&rdquo The latest advances within the research impetus of synthetic biology, which has been developed with zeal in recent years, give rise to expectations that there will soon be more news from this code. This is particularly the case since one of the objectives of this subdiscipline of biology is precisely to produce microbial forms of life with properties that do not occur in nature. In the wake of such research, old ethical and philosophical issues, expectations and anxieties arise again in acute new forms.


The first isolated references to the term &ldquosynthetic biology&rdquo can be identified as early as the beginning of the twentieth century. For instance, the French medical scientist and biologist Stephane Leduc published a book in 1912 entitled &ldquoLa Biologie Synthétique.&rdquo [2] In this volume, Leduc maintained that, besides the method of analysis, fact compilation and classification, there also existed in science a synthetic method that attempts to reproduce observed phenomena in a rule-governed and reproducible manner. According to Leduc, a science can only develop in its entirety if this second method is acknowledged and employed. In his era of biology, Leduc felt that the consistent implementation of this scheme of the controlled reproduction of observations was missing, and he advocated such an application. It can thus be said that the conviction&mdashaccording to which the task of theory is primarily to deliver knowledge that enables the object of theoretical reflection to be controlled and utilised&mdashis transferred to the area of living things in Leduc&rsquos first attempts. Knowledge, and therefore also biological knowledge, can only accurately be called such if it enables objects to be controlled and applied practically, since knowledge is only confirmed in this manner. This, at least, is one way in which this assumption, central to the modern natural sciences, can be stated.

In 1911, the biologist Jacques Loeb, who lectured in germany and the U.S.A., formulated his hypotheses in a similar fashion:

[it] must be emphasised that modern biology is a purely experimental science, the results of which can take only one of two possible forms: either we succeed in controlling a life phenomenon to the extent that we can evoke the same whenever we wish (for example, muscle twitches or the chemical stimulation of the development of certain mammals&rsquo eggs) or else we manage to identify the numerical connection between an experimental condition and the biological result (such as in the Mendelian law). [3]

The prerequisite of this natural science-based understanding of biology is that the phenomena of living things can be completely reduced to simple powers and laws that govern the organism and whose modes of action can be clearly predicted. Applied to the question of how life can evolve, this assumption must lead to the requirement that living things must be artificially producible. Entirely in this spirit and typically for his era, [4] in 1906 Jaques Loeb declared &ldquoabiogenesis&rdquo&mdashthe creation of life from inanimate material&mdashto be an objective of biology. [5] John Butler Burke, an English biologist, also believed that there must be a transition from that deemed inanimate to that considered animate he describes the experimental production of &ldquoanimalcules&rdquo as a task of biology. [6]

These early scientific/programmatic approaches to &ldquosynthetic&rdquo&mdash i.e., &ldquoassembling&rdquo or &ldquoproducing&rdquo&mdashbiology illustrate the fact that the technical realisation of each body of knowledge is not a contingent ingredient in that knowledge understood to be natural science, but rather a constitutive part of this research. The reproducible application is the confirmation of the findings gained from analysis, and hence not only the result but simultaneously the catalyst of research. In this general sense, synthetic biology is not &ldquomerely&rdquo a branch of biological research alongside many others, but is an essential element of science-based biology. Its existence is an expression of the fact that biology has established itself as a programmatic natural science, and moreover complies methodologically with the respective requirements. This orientation towards the replication and recreation of nature, which makes the ability to control living things the central research objective and the central test for knowledge advancement, is also described in later literature as the &ldquoengineering science viewpoint&rdquo or the &ldquoengineering science ideal.&rdquo [7]

At the level of intra- and intercellular molecular processes, this scheme could only be developed systematically after the discovery of the DNA double helix. Following this milestone, the term &ldquosynthetic biology&rdquo was also swiftly applied again in this area of molecular biology, where its meaning was used analogously to that found at the beginning of the century. Thus, in 1974 the PolishAmerican geneticist and molecular biologist Waclaw Szybalski wrote in terms that sound almost prophetic from today&rsquos perspective: &ldquoup to now we are working on the descriptive phase of molecular biology. . . . But the real challenge will start when we enter the synthetic biology phase of research in our field. We will then devise new control elements and add these new modules to the existing genomes or build up wholly new genomes. This would be a field with the unlimited expansion potential and hardly any limitations to building &lsquonew better control circuits&rsquo and . . . finally other &lsquosynthetic&rsquo organisms.&rdquo [8]

Four years later, in 1978, marking the occasion of the awarding of the Nobel prize in Physiology and Medicine, Szybalski and Skalka wrote an editorial in the journal gene that displayed a very similar set of assumptions. The pair proclaimed the dawn of a new era in biology: the work on restriction nucleases not only permits us easily to construct recombinant DNA molecules and to analyze individual genes but also has led us into the new era of &ldquosynthetic biology&rdquo where not only existing genes are described and analyzed but also new gene arrangements can be constructed and evaluated. [9]

The final step on the road toward current developments involves endeavors to establish the field of &ldquosynthetic biology,&rdquo which commenced at around the year 2000. In continuation of the molecular biological research approach described by Szybalski, a group of American researchers defined synthetic biology as a scientific activity that aims to analyze the interactions of complex cellular processes at the molecular level and to test these analyses by modelling and replicating the processes and structures, and to make them technically utilizable. Thanks to a close connection between biology and engineering science, an attempt is therefore made at conducting genetic engineering, previously characterised as being &ldquomanual,&rdquo in a more systematic manner and on a greater scale&mdashdespite its analytical foundation and its synthetic realization. [10]

This more recent approach in establishing the discipline of synthetic biology has been inspired and supported by the increase in knowledge in the area of systems biology on the one hand, and on the other, and primarily, by the quick-paced development of electronics, rapidly improving sequencing technology and the possibilities offered by DNA synthesis, which is becoming increasingly cheaper and more accessible. [11] gene sequences no longer need to be synthesized in the laboratory by the scientists themselves, but can be ordered via e-mail from specialist companies and dispatched by mail. Prices for sequencing a base pair are constantly decreasing, while the length of the gene sequences that can be synthesized is increasing. [12] It is impossible to forecast an end to this development. One thing is clear, though. With these technical and economic foundations there are also greater possibilities for more easily testing hypotheses about how the molecular building blocks of simple organisms function with regard to their application and reproduction. Accordingly, the possibilities for replicating or recreating gene sequences and genomes have also burgeoned.

Synthetic Biology&rsquos Scope of Research

With regard to current research within the field of synthetic biology, a distinction can be drawn between two ways in which attempts are being made to achieve the overarching research objectives. Some approaches aspire to produce a single-cell organism or a cell in the laboratory from scratch, from non-living molecules. Other approaches attempt to minimize the genome of an existing bacterium to such an extent that the organism is only left with the above basic properties of life, with no further specific abilities. The aim of &ldquohollowing out&rdquo existing bacteria, in other words, is, if possible, to leave the organism with only those genes that ensure the organism&rsquos metabolism and fertility&mdashand that are capable of mutating. According to the basis from which the minimal cell or minimal organism is set to be developed, the two main directions of research can be separated into &ldquotop-down&rdquo and &ldquobottom-up&rdquo or &ldquoin vivo&rdquo and &ldquoin vitro&rdquo approaches of synthetic biology.

The advanced idea of the top-down approach is to add genome sequences, assembled as the need arises, to the engineered minimal organism so that it can perform precisely defined tasks. The basic organism would act as a &ldquochassis,&rdquo to which the desired functions are added. [13] In this context, the genomes are often called the &ldquosoftware,&rdquo while the remaining structures of the organism are described as &ldquohardware.&rdquo Following genetic essentialism (which is a disputed perspective outside of the field of synthetic biology), it can be said that the aim of the top-down approach is to equip the hardware of a cell with new, tailor-made software, designed to control it.

On the other hand, the aim of the de novo production of a so-called minimal cell in the laboratory, the paradigmatic case of the bottom-up approach, is to assemble a basic form of life from simple parts. In doing so, no existing organism is used and altered in vivo. Instead, an organism or, in general, a biological system is created in vitro from scratch. This second approach can in turn be subdivided into those approaches that deploy already existing biological building blocks to assemble the artificial or &ldquosynthetic&rdquo cell, and those approaches that attempt to develop a kind of &ldquoprotocell&rdquo (or cell analogue, rather than actual cell) and which set out with chemical precursors. [14] The typical feature of these two research approaches is that they do not only comprise the pure replica of natural cells, but also envisage the construction of cells whose mechanisms for realizing the functions of life are very different from naturally occurring cells. Where the latter is the case, reference is also made to engineering an &ldquoorthogonal&rdquo nature. In this context, and following the parlance of information science, &ldquoorthogonal&rdquo means biological systems whose basic structures are so dissimilar to those occurring in nature that they can only interact with them to a very limited extent, if at all.

The top-down (or in vivo) and bottom-up (or in vitro) approaches are typically associated with two differing research interests and research traditions. While the in vivo approach is primarily oriented towards technical application and easily tolerates an engineering-based access to modularisation and standardisation, the in vitro approach is more akin to fundamental research that aims to explain and reconstruct the origin and basic functions of life. The foundation and driving force behind this research is the question of how the origin of life can be explained and reproduced in the course of natural history. Nonetheless, this approach is also related to issues of application within the context of synthetic biology. It cannot be ruled out that an in vitro created cell analogue may turn out to be more suitable than a minimal bacterium as a basis for technical realizations.

Although this classification of the research landscape of synthetic biology is useful in obtaining an initial overview, it must nevertheless be emphasised that a range of research approaches exist that cannot be neatly fit into this classification scheme. This is particularly the case for all types of research that deal with the analysis and the replication and regeneration of metabolic processes and cellular signal structures. In these cases, research involves analysing and replicating how cellular constituents in which the genome is embedded function. These studies will in all likelihood have to be counted among the in vivo approaches, which also follow the top-down procedure in that&mdashin analysis and synthesis&mdashthey seek to split up complex biological structures into easily describable sub-areas. However, this type of investigation does not generally aim to engineer a minimal bacterium in this respect, this kind of research distances itself from the top-down procedure, which is otherwise frequently deemed typical for in vivo approaches.

This difference can also be illustrated with regard to the use of the imagery of hardware and software in the minimal bacterium project. Inquiry into understanding metabolic pathways and signal transmission mechanisms cannot be focussed on the conception of the genome as the software of the cell and the remaining biological cell structures as the hardware due to the fact that it becomes clear from such imagery that these remaining structures are also integrally involved in the behavior that an organism ultimately has. Moreover, these structures can also be used to control the behavior of organisms in a similar fashion to the genome. It is not improbable that this kind of research into cell functions, &ldquobeside the genome,&rdquo will also lead to technologically far-reaching developments. Synthetic biology as a whole is thus more complex than what can readily be portrayed in the media, which already tends to reinforce genomic reductionism and to focus on the major projects of the bottom-up and top-down models that can be conveyed more succinctly.

Finally, a further area of research exists within synthetic biology that is slightly out of line with the top-down and bottomup framework. This area of research involves the attempt to create genetic structures that are not founded on the same material basis as those occurring in nature. There are thus approaches to supplement the four natural base pairs of the genome with additional base pairs, and other research is being carried out that goes one step further and tries to create genomes that function completely independently of the four base pairs of natural life. In the first instance, such approaches belong to the in vitro field of synthetic biology since the synthetic genomes are assembled from simple building blocks. They therefore blend in, and are partly also a direct element of research within the context of engineering a minimal cell. However, it is also conceivable that non-natural genomes can be used in natural cells and organisms&mdashin other words, to deploy them in vivo.

Specific Characteristics

In order to grasp the specific ethical and philosophical challenges of a newly emerging direction of research, it is essential to ascertain in precise terms how this science differs from already existing areas of science. What, in other words, is novel about synthetic biology?

Application-oriented sciences&mdashto which synthetic biology belongs&mdashare generally subdivided into &ldquoenabling technologies&rdquo (which create the prerequisites for realizing the respective research), &ldquobasic development technologies,&rdquo and &ldquoapplied technologies.&rdquo In the case of synthetic biology, the technological prerequisites mainly include gene synthesis technologies, the possibilities of which are constantly expanding. The field of research consisting of in vivo and in vitro approaches and the research surrounding these paradigmatic cores form the area of basic development. The applied technologies include all technical applications that are conceivably associated with synthetic biology. Out of these three areas, the technological prerequisites and the basic development are primarily of interest when exploring the question of what is novel about synthetic biology.

As our brief tour of the history of the subject has already demonstrated, synthetic biology is not a topic that has emerged &ldquoout of the blue.&rdquo On the whole, there are continuities and mechanisms internal to science that have facilitated the emergence of today&rsquos synthetic biology moreover, in miniature there are also many specific points of contact to existing areas of research. The main points of contact are gene technology and systems biology, as well as engineering science, information technology, and nanotechnology. Due to these manifold references, some commentators consider synthetic biology to be almost a prime example of the much-evoked &ldquoconverging sciences.&rdquo [15] In particular, the vicinity to genetic engineering leads to the justified critical question of what is actually novel about synthetic biology and, concurrently, whether this science implies new ethical challenges.

In the first instance, this question can only be answered using quantitative references: in the area of technological prerequisites, the capabilities of gene synthesis are increasing up to the ability to synthesize entire genomes. In the area of basic development, depending on the research direction, the aim is not simply to replace or modify individual gene sequences of an existing organism but to insert a whole synthesized genome into a genetically minimised bacterium. As we have already seen, research is also be carried out into replicating metabolic cell processes and signal transmission mechanisms, and supplementing the &ldquoalphabet of life&rdquo&mdashcomprising four different organic bases&mdashwith other bases, or else completely replacing them and incorporating non-natural amino acids into synthetic organisms.

For this reason, there has been a noticeable extension of that which is technically manipulable and controllable. With the synthesis of larger genomes and the advent of also being able to handle large gene fragments, it is no longer only individual, short DNA segments, but also entire genomes that come into practical reach. [16] For instance, scientists recently managed to synthesize the entire genome of Mycoplasma genitalium, a DNA structure with over 580,000 building blocks&mdasha significant difference to the classic gene technological synthesising of a plasmid with 5,000 elements. [17] Gene technological research, such as transplanting parts of the human immune system to mice in order to produce human antibodies [18] and implanting beta carotene synthesis into rice, [19] are being continued and quantitatively expanded in this manner. Furthermore, as already mentioned, the genome is being expanded with novel starting materials and recreated in research into synthetic biology. In addition, other molecular cell structures beside the genome are being replicated, making them controllable.

In the ethics of technology there is a meaningful distinction to be made between quantitative and qualitative change change in degree and change in kind. Quantitative change extends the scope of pre-existing human power and control qualitative change ushers in a new kind or dimension of power and control. Taken individually, new characteristics of synthetic biology appear to represent a quantitative rather than qualitative advance. However, when viewed on the whole it can be maintained that synthetic biology opens a new field of research and technology from a qualitative perspective, even if it is impossible to define where the transition from quantity to quality lies exactly. The crucial element of this transition is that the focus on the organism to be explored and controlled is changing. The basis of gene technological manipulations is an existing organism with properties that are of keen interest to humans. These existing properties are then optimised by genetic engineering to make them economically exploitable. However, the perspective of synthetic biology is no longer necessarily oriented towards existing organisms. Since, for synthetic biology, the entire genome and the whole molecular structure of single-cell organisms are technically configurable, therefore existing organisms and existing properties are ultimately only incidental examples of what can be assembled from the building blocks of nature. If scientists seek an organism to serve certain interests, the ideal of synthetic biology is specifically to design and engineer these organisms according to these interests.

In the case of synthetic biology, therefore, the phenomenon of single-cell life&mdashor indeed of life at the cellular level&mdashis made accessible to human manipulation and design never seen before. While genetic engineering was linked to already existing forms of life and the exchange of single gene sequences, synthetic biology goes about creating and engineering forms of life that are largely detached from nature. Hand-in-hand with a manufacturing process that, according to ambition, will be characterised by computer simulation and construction, modularisation and standardisation, synthetic biology will henceforth initiate a change in perspectives from genetically engineered manipulation to synthetic creation, which can be fairly described as a qualitative leap.

This leap can be illustrated using the example of a scientific competition that has developed with the emergence of the latest initiatives at establishing synthetic biology: the &ldquoInternational Genetically Engineered Machines&rdquo competition (IGEM) was initiated by the Massachusetts Institute of Technology in 2003. In 2009, 112 teams and a total of approximately 1,200 participants entered the competition. [20] In it, young scientists and students design and develop DNA-based biological circuits, proteins with non-natural properties or artificial cell&ndashcell communication or signal transduction processes.

A requirement for participation is that the genetic modules engineered for the competition have to possess compatible terminals to facilitate the quick assembly of various modules. Furthermore, these modules must be deposited in a material bank, the so-called BioBricks database. Not only contestants can access this database&mdashother interested parties can also access it and contribute towards its expansion. [21]

This material bank is to be used as a building set geared towards simplifying and accelerating the future development of increasingly complex synthetic biological systems. Genetic building blocks will no longer be manipulated and replaced ad hoc in individual cases, as is the convention in genetic engineering, but rather will be specifically developed and made accessible in the form of standardised building blocks (it is no coincidence that they have been christened &ldquoBioBricks&rdquo analogous to Lego bricks) to perform specific tasks.

In this way, the IGEM competition highlights two central concepts on which synthetic biology is founded. On the one hand, the great extent to which synthetic biology is replacing the old gene technological method of improving that which already exists becomes apparent through the creation of new things&mdashphenomena which are to fulfil precisely defined tasks that no known natural organism can even remotely achieve. On the other hand, it becomes clear how much the interference of synthetic biology in nature relies on the modularisation and compatibility of the generated biological systems.

Some Ethical Remarks

Ethical reflection on synthetic biology has so far mostly been concerned with issues of biosafety and biosecurity. [22] These topics are indispensable if one is concerned about short- or medium-term legal or political regulations. Nonetheless, in order to get a hold on ethically relevant hidden dynamics of the research agenda, a complementary, moregeneral approach to ethical issues is essential. [23] Given the specific historical and systematic background of synthetic biology described above, a number of relevant issues can be discerned, all of them hinging on the way in which synthetic biology approaches the phenomenon of life.

Synthetic biology fits an ideal of scientific progress in which scientific explanations of the behavior of complex entities are based on explanations of the behavior of those entities&rsquo parts. If one is to find an explanation of the actions and reactions of an organism, one is led to look for explanations in terms of patterns of actions and reactions of the molecular make-up of the organism. In this way, synthetic biology follows genetic engineering&rsquos epistemology, apparently giving further credentials to its aspirations by adding the ability of creation to genetic engineering&rsquos manipulative abilities.

This explanatory strategy stands in contrast to explanations that refer to an organism&rsquos perceptions of and attempts to accommodate to its environment, since in this latter case states of the organism as a whole are taken to be able to influence processes at cellular or molecular level. Taking human beings as an example, the contrast is obvious. One may explain the behavior of a human being by referring to genetic determinants or, alternatively, to his or her perceptions and intentions. While the former knowledge can be used as a tool to identify Archimedean points of behavior manipulation, the latter kind of knowledge is the prerequisite of the ability to talk to and understand the person as a whole person and to ascribe inherent value to it.

Now, if the organism is a single cell, one may assume that the two perspectives converge. After all, what can the ability to &ldquotalk to a cell&rdquo conceivably mean besides being able to manipulate cellular features? This is the reason why metaphors of signaling and sensing, often used in molecular biology without recognizing the tension between these concepts and bottom-up explanations, can be understood as containing a core of truth, although they are often criticized as misleading. Making use of molecular processes inside a single cell organism may be seen as a way of &ldquotalking&rdquo to the organism in this special case.

Nonetheless, the perspective of &ldquotalking&rdquo basically draws one&rsquos attention in other directions than does the bottom-up outlook, even in the case of single cell organisms. For example, if a cell is understood as sensing and transmitting information, the influence of the environment on processes inside the cell becomes a natural part of explanation of what the cell does, yet, when working within the bottom-up paradigm, the cellular environment appears to be a subordinate factor of influence. Accordingly, the bottom-up paradigm favors research on genetics and tends to construe the influence of genetic processes on the organism as deterministic, whereas the &ldquoresponsive organism outlook&rdquo stresses the organism&rsquos ability to accommodate to its surroundings, including the ability to remake itself in this process.

It is commonly supposed that in moving upward from simple to ever more complex forms of life genetic bottom-up explanations give way to &ldquoresponsive organism&rdquo explanations, necessitated by emerging phenomena such as sensitivity, consciousness, rationality, etc. It is important to note, though, that no matter how complex a form of life is, it is always possible to maintain the ideal of a bottom-up explanation. unexpected behavior that may seem to renounce this ideal can always be explained away by referring to the complexity of causes and effects involved&mdasha complexity that is not yet accounted for, but will in the future be accessible in terms of bottom-up explanations.

Moreover, it is difficult to see how &ldquoresponsive organism&rdquo explanations are to be based on bottom-up explanations, given that the explanatory principles involved stand in stark contrast to each other. To invoke &ldquoemergence&rdquo as a solution to this problem is simply to invoke an explanatory &ldquodeus ex machina.&rdquo Hence, if one wants to allow &ldquoresponsive organism&rdquo explanations to play a role in explaining behavior at all, one has to use this scheme right from the start, in accounts of even the simplest forms of life.

Now this does not mean that bottom-up explanations are generally useless and ought to be avoided. For one thing, in the case of simple forms of life, the languages of the two schemes may overlap to a certain degree. For another, the bottom-up outlook can always serve as a tool for any inquiry that is aiming at effectively controlling and manipulating processes. It does mean, though, that in accepting the general validity of the &ldquoresponsive organism&rdquo perspective one ought to be attentive to explanations even in the case of simple forms of life. One should also be attentive to the ethical limits the &ldquoresponsive organism&rdquo outlook imposes on bottom-up explanations if applied to higher organisms&mdashespecially, of course, to human beings.

Everything that has been said so far applies almost equally to genetic engineering and synthetic biology. Therefore, in order to delineate specific ethical aspects of synthetic biology, one has to take a further step and look at synthetic biology&rsquos special features, i.e., first and foremost, the appeal to creation and, to a lesser degree, the role of engineering principles such as modularization and standardization.

Creation, from the point of view of synthetic biology, amounts to being able to put together basic cellular parts, thus building a novel entity that exhibits all the characteristics of life. This is true both of in vivo and in vitro approaches. As an obvious first remark, it is important to note that this kind of creative activity is not &ldquocreatio ex nihilo,&rdquo creation from nothing. [24] In other words, synthetic biology&rsquos creations cannot unqualifiedly be compared to the act of creation that theology commonly attributes exclusively to god&mdashclaims to this effect both by scientists and by synthetic biology&rsquos critics notwithstanding. Even if it became possible, following a bottom-up approach, to build a living cell entirely from non-living complex molecules, this still would have to count as creation by way of refined combination of given parts. One may say that in this scenario, too, scientists do not create life from scratch but supply necessary and sufficient conditions for matter to actualize its potential to form living organisms.

Now, while the assertion to be able to create life from scratch surely must count as hyperbolic, it seems to be true that synthetic biology is a more creative activity than genetic engineering has been before. The aim and the success of the IGEM competition bear witness to the fact that synthetic biology carries with it a new level of aspiration, if not yet achievement. Whereas genetic engineering had its focus on optimizations of existing organisms (the benchmark being societal or consumer needs and preferences), synthetic biology gives free play to fantasy and imagination. Potentially, synthetic biology takes us beyond nature. &ldquoNature 2.0,&rdquo i.e., nature with novel functions or even an orthogonal system of life, is not pure speculation any more.

From an ethical perspective, the shift of perspectives is significant, since the results of the creative activity in question gain life of their own. Synthetic organisms interact with the environment and evolve just like natural organisms, which means that their future is to a large extent unpredictable. At the same time, the engineering ideal of synthetic biology suggests quite the opposite, namely a product that, since it can be created, can be understood and explained in all the details of its functioning. Condensed to a catchword, synthetic biology reconstructs and creates organisms as machine-like entities, while nonetheless as a matter of fact having to cope with all the uncertainties and idiosyncrasies of evolving life.

From this perspective it does not come as a surprise that in the cultural imagination closely connected to synthetic biology&rsquos aim of creation of life are the stories of Frankenstein&rsquos creature and Faust&rsquos Homunculus. Both stories may be taken to exemplify, among many other aspects, the gap between the highest accomplishment that science can aspire to, namely, the creation of living organisms and essential autonomy of these organisms, which turns them into independent rivals and, in the case of Frankenstein, victims of their creators. In other words, Frankenstein and Faust are not always misguided associations of a scientifically under-educated public. Rather, these cultural narratives and cautionary tales can help us to stay aware of the limits of the general explanatory framework synthetic biology employs and to the necessity of sober multi-disciplinary risk assessment.


Synthetic biology is a rapidly developing new field of biological research. Its aims to analyze intra- and intercellular processes and to use this knowledge in order to build hitherto unknown singlecell life forms. Thus, the shift from analysis to synthesis to which chemistry has been subject in the early twentieth century is now about to become reality in biology.

In the case of chemistry, this shift has had a massive influence on the economy and society as a whole. It does not come as a surprise, then, that the rise of synthetic biology is accompanied by high-flying expectations: possible applications range from decisive advances in cancer therapy to microorganisms that degrade remedies and fuel-producing bacteria.

At the same time, the development of the research field is met by a growing number of critical voices. Under the heading of &ldquobiosafety,&rdquo social scientists, ethicists, and philosophers discuss topics concerning the unintended harmful effects of synthetic organisms to humans and the environment, and further attention is paid to possible cases of intended misuse&mdashso-called biosecurity concerns. Taking a step back, it becomes possible in addition to focus on some general ethical implications of synthetic biology&rsquos endeavor.

First, calling an object alive is deeply connected, both historically and systematically, with the conviction that the object in question is to be valued as a (more or less) autonomous agent, a status that artifacts do not share. As a consequence, the way in which newly created organisms are conceptualized has an ethical impact on how life in general is understood and valued. When describing microorganisms and their signaling pathways, synthetic biology researchers often invoke computer metaphors of &ldquohardware&rdquo and &ldquosoftware&rdquo as well as mechanical metaphors of &ldquobrick&rdquo and &ldquochassis.&rdquo Keeping in mind the difficulties of defining life and the normative dimension of the concept of life, it is important, though, not to prematurely conflate the concepts of &ldquolife&rdquo and &ldquomachine&rdquo in synthetic biology research.

Second, even though it is not correct to claim that synthetic biology attempts to create life &ldquofrom scratch,&rdquo synthetic biology does comprise a perspective of creation rather than manipulation. From point of view of creation, one does not have to settle for smoothing out nature&rsquos shortcomings but can engineer a nature without shortcomings from scratch. Using the abilities of nature through cultivation, manipulation or even exploitation differs from reinventing nature. Assuming all appropriate safety measures are in place, doing so might be justifiable in many specific cases. Nonetheless, taken as a general approach, it might lead to an overestimation of how well we understand nature&rsquos processes and our own needs and interests and of how best to achieve them.

Following up on this last point, it becomes possible to connect ethical reflections on life and creation with down-to-earth questions of biosafety and biosecurity. For example, given the ability to create single new forms of life, the degree to which we believe in our ability to understand and calculate nature&rsquos processes will increase, while at the same time our actual knowledge of complex interactions of different kinds of organisms in their habitat might not have expanded at all. As a consequence, the core characteristics&mdashethically speaking&mdashof synthetic biology present a challenge to regulations and treatises originally developed to deal with risks and cases of misuse regarding genetic engineering.

[1]. B.J. Yeh and W.A. Lim, Synthetic Biology: Lessons from the History of Synthetic Organic Chemistry, Nat Chem Biol 3(9), 2007, pp. 521-525.

[2]. S. Leduc, La Biologie Synthétique. Paris, 1912.

[3]. J. Loeb, Das Leben. Leipzig, 1911, p. 6.

[4]. E.F. Keller, Making Sense of Life. Explaining Biological Development with Models, Metaphors, and Machines, Cambridge, MA: Harvard University Press, 2002, p. 19.

[5]. J. Loeb, The Dynamics of Living Matter, New York, 1906, p. 223.

[6]. J.B. Burke, The Origin of Life. Its Physical Basis and Definition. London, 1906, p. 5.

[7]. P.J. Pauly, Controlling Life. Jacques Loeb and the Engineering Ideal in Biology. New York, 1987 R.P. Shetty, D. Endy, et al., &ldquoEngineering BioBrick Vectors from BioBrick Parts,&rdquo J Biol Eng 2(1), 2008, p. 5.

[8]. W. Szybalski, &ldquoIn Vivo and In Vitro Initiation of Transcription,&rdquo Adv Exp Med Biol 44(1), 1974, pp. 23-24.

[9]. W. Szybalski, A. Skalka, &ldquoNobel Prizes and Restriction Enzymes,&rdquo Gene 4(3), 1978, pp. 181-182.

[10]. S.A. Benner, A.M. Sismour, &ldquoSynthetic Biology,&rdquo Nat Rev Genet 6(7), 2005, pp. 533-543.

[11]. R. Carlson, &ldquoThe Pace and Proliferation of Biological Technologies,&rdquo Biosecurity and Bioterrorism: Biodefense Strategy, Practice, and Science 1(3), 2003, pp. 203-214.

[12]. Etc. Group, &ldquoExtreme Genetic Engineering. An Introduction to Synthetic Biology,&rdquo, 2007, p. 10.

[13]. D.A. Drubin, J.C. Way, P.A. Silver, &ldquoDesigning Biological Systems,&rdquo Genes Dev 21(3), 2007, pp. 242-254 P. Fu, &ldquoA Perspective of Synthetic Biology: Assembling Building Blocks for Novel Functions,&rdquo Biotechnol J 1(6), 2006, pp.690-699.

[14]. A.C. Forster, G.M. Church, &ldquoSynthetic Biology Projects In Vitro,&rdquo Genome Res 17(1), 2007, pp. 1-6 P.L. Luisi, &ldquoChemical Aspects of Synthetic Biology,&rdquo Chem Biodivers 4(4), 2007, pp. 603-621 P.L. Luisi, F. Ferri, P. Stano, &ldquoApproaches to Semi-synthetic Minimal Cells: A Review,&rdquo Naturwissenschaften 93(1), 2006, pp. 1-13.

[15]. Etc. Group, &ldquoExtreme Genetic Engineering,&rdquo p. 5.

[16]. M. Itaya, et al., &ldquoBottom-up Genome Assembly Using the Bacillus subtilis Genome Vector,&rdquo Nat Methods 5(1), 2008, pp. 41-43.

[17]. D.G. Gibson, et al., &ldquoComplete Chemical Synthesis, Assembly, and Cloning of a Mycoplasma genitalium Genome,&rdquo Science 319(5867), 2008, pp. 1215-1220.

[18]. A. Jakobovits, et al., &ldquoFrom XenoMouse Technology to Panitumumab, the First Fully Human Antibody Product from Transgenic Mice,&rdquo Nat Biotechnol 25(10), 2007, pp. 1134- 1143.

[19]. P. Beyer, et al., &ldquoGolden Rice: Introducing the Beta-carotene Biosynthesis Pathway into Rice Endosperm by Genetic Engineering to Defeat Vitamin A Deficiency,&rdquo J Nutr 132(3), 2002, pp. 506-510.

[22]. J.B. Tucker and R.A. Zilinskas, &ldquoThe Promise and Perils of Synthetic Biology,&rdquo The New Atlantis 12, 2006, pp. 25-45 M. Schmidt, A. Ganguli-Mitra, et al., &ldquoA Priority Paper for the Societal and Ethical Aspects of Synthetic Biology,&rdquo Syst Synth Biol 3(1-4), 2009, pp. 3-7.

[23]. S. Yearley, &ldquoThe Ethical Landscape: Identifying the Right Way to Think about the Ethical and Societal Aspects of Synthetic Biology Research and Products,&rdquo J R Soc Interface 2009, doi: 10.1098/rsif.2009.0055.focus J. Boldt, O. Müller, &ldquoNewtons of the Leaves of Grass,&rdquo Nat Biotechnol 26(4), 2008, pp. 387-389.

[24]. P. Dabrock, &ldquoPlaying God? Synthetic Biology as a Theological and Ethical Challenge,&rdquo Syst Synth Biol 3(1-4), 2009, pp. 47-54.

Joachim Boldt

Joachim Boldt studied philosophy, literature, and linguistics in Heidelberg, Berlin, and Sheffield. He obtained a PhD in philosophy in Berlin, his dissertation was on Kierkegaard's Fear and Trembling. As postdoc he was affiliated with the Department of Medical Ethics and the History of Medicine at Freiburg University.

Mathematical proof for the designer requirement

That a complex structure such as a living organism could be formed by chance without intelligent input has never been demonstrated in the lab or anywhere else. Given enough time, the naturalistic worldview reasons, anything is at least possible. The problem with this view is that the degree of information and complexity required for living organisms to be able to “live” is such that, aside from deliberate intelligent design, from what we know now, no matter what the conditions, time alone will not allow for the naturalistic construction of life. Evolutionist Stephen Jay Gould stated that even if evolutionary history on earth repeated itself a million times, he doubts whether anything like Homo sapiens would ever develop again (Gould, 1989 also see Kayzer, p. 86, 1997).

Many researchers have concluded that the probability of life arising by chance is so remote that we have to label it an impossibility. For example, Hoyle (1983) notes that the probability of drawing either ten white or ten black balls out of a large box full of balls that contains equal numbers of black and white balls is five times out of one million! If we increase the number to 100 and draw sets of 100 balls, the probability of drawing 100 black or 100 white balls in succession is now so low as to be for all practical purposes impossible.

To illustrate this concept as applied in biology, an ordered structure of just 206 parts will be examined. This is not a large number—the adult human skeleton, for example, contains on the average 206 separate bones, all assembled together in a perfectly integrated functioning whole. And all body systems—even our cells’ organelles—are far more complex than this.

To determine the possible number of different ways 206 parts could be connected, consider a system of one part which can be lined up in only one way (1 x 1) or a system of two parts in two ways (1 x 2) or 1, 2 and 2, 1 a system of three parts, which can be aligned in six ways (1 x 2 x 3), or 1, 2, 3 2, 3, 1 2, 1, 3 1, 3, 2 3, 1, 2 3, 2, 1 one of four parts in 24 ways (1 x 2 x 3 x 4), and so on. Thus, a system of 206 parts could be aligned in 1 x 2 x 3 … 206 different ways, equal to 1 x 2 x 3 … x 206. This number is called “206 factorial” and is written “206!”.

The value 206! is an enormously large number, approximately 10 388 , which is a “1” followed by 388 zeros, or:


Achievement of only the correct general position required (ignoring for now where the bones came from, their upside-down or right-side-up placement, their alignment, the origin of the tendons, ligaments, and other supporting structures) for all 206 parts will occur only once out of 10 388 random assortments. This means one chance out of 10 388 exists of the correct order being selected on the first trial, and each and every other trial afterward, given all the bones as they presently exist in our body.

If one new trial could be completed each second for every single second available in all of the estimated evolutionary view of astronomic time (about 10 to 20 billion years), using the most conservative estimate gives us 10 18 seconds the chances that the correct general position will be obtained by random is less than once in 10 billion years. This will produce a probability of only one out of 10 (388–18) or one in 10 370 .

If each part is only the size of an electron, one of the smallest known particles in the universe, and the entire known universe were solidly packed with sets of bones, this area conservatively estimated at 100 billion cubic light years could contain only about 10 130 sets of 206 parts each. What is the possibility that just one of these 10 130 sets, each arranging their members by chance, will achieve the correct alignment just once in ten billion years? Suppose also that we invent a machine capable of making not one trial per second, but a billion-billion different trials each second on every single one of the 10 130 sets. The maximum number of possible trials that anyone could possibly conceive being made with this type of situation would permit a total of 10 166 trials (10 130 x 10 18 x 10 18 ). Even given these odds, the chance that one of these 10 166 trials would produce the correct result is only one out of 10 388 , or only one in 10 222 trials for all sets.

Further, all the parts must both first exist and be instantaneously assembled properly in order for the organism to function. For all practical purposes, a zero possibility exists that the correct general position of only 206 parts could be obtained simultaneously by chance and the average human has about 75 trillion cells! The human cerebral cortex alone contains over 10 billion cells, all arranged in the proper order, and each of these cells is itself infinitely complex from a human standpoint. Each of the cells in the human body consists of multi-thousands of basic parts such as organelles and multi-millions of complex proteins and other parts, all of which must be assembled both correctly and instantaneously as a unit in order to function. This required balance and assembly must be maintained even during cell division.

This illustration indicates that the argument commonly used by evolutionists “given enough time, anything is possible” is wanting. Evolutionary naturalism claims that the bone system happened as a result of time, luck, and “natural” forces, the last element actually holding the status of a god . Time, the chief escape that naturalism must rely on to support its theory, is thus a false god . Complex ordered structures of any kind (of which billions must exist in the body for it to work) cannot happen except by design and intelligence, and they must have occurred simultaneously for the unit to function. Scientists recognize this problem, and this is why Stephen Jay Gould concluded that humans are a glorious evolutionary accident which required 60 trillion contingent events (Gould, 1989, see also Kayzer, p. 92, 1997).

Of course, the naturalistic evolution assumption does not propose that the parts of life resulted from an assembly of bones, but instead proposes that an extended series of stepwise coincidences gave rise to life and the world as we know it. In other words, the first coincidence led to a second coincidence, which led to a third coincidence, which eventually led to coincidence “i,” which eventually led up to the present situation, “N.” Evolutionists have not even been able to posit a mechanistic “first” coincidence, only the assumption that each step must have had a survival advantage and only by this means could evolution from simple to complex have occurred. Each coincidence “i” is assumed to be dependent upon prior steps and to have an associated dependent probability “Pi.” The resultant probability estimate for the occurrence of evolutionary naturalism is calculated as the product series, given the following:

N the number of stepwise coincidences in the evolutionary process
i = the index for each coincidence: i = 1,2,3 …
Pi the evaluated dependent probability for the i’th coincidence
PE = the product probability that everything evolved by naturalism.

Innumerable steps are postulated to exist in the evolutionary sequence, therefore N is very large (i.e., N …). All values of Pi are less than or equal to one, with most of them much smaller than 1. The greater the proposed leap in step i, the smaller the associated probability Pi 1, and a property of product series where N is very large and most terms are significantly less than one quickly converges very close to zero.

The conclusion of this calculation is that the probability of naturalistic evolution is essentially zero. Sir Fred Hoyle (1982) calculated “the chance of a random shuffling of amino acids producing a workable set of enzymes” to be less than 10 40,000 , and the famous unrealistically optimistic Green Band equation gives the chance of finding life on another planet in the order of only one in 10 30 .

These probabilities argue that the chance distribution of molecules could never lead to the conditions favorable for the spontaneous development of life. The reasoning that leads us to this conclusion is that living molecules contain a large number of elements which must be instantly assembled in a certain order for life. The probability of the required order in a single basic protein molecule arising purely from chance is estimated at 10 43 (Overman, 1997). Since thousands of complex protein molecules are required to build a simple cell, probability moves chance arrangements of these molecules outside the realm of possibility. The smallest proteins have an atomic mass of 100,000 or more atomic mass units (AMU), which is equal to 100,000 hydrogen atoms (Branden and Tooze, 1991). And this calculation evaluates only the necessary order of parts, not a functional arrangement, i.e., one that works. Even if the gears of a clock are arranged in the correct order, the clock will not function properly until the gears are properly meshed, spaced, adjusted, the tolerances are correct, and the system is properly secured.

A problem with understanding the concept “life” is that although we now have identified many of the chemicals which are necessary, researchers do not yet know all of the factors necessary for life “to live.” Further, even assembling the proper chemicals together does not produce life. The proper arrangement of amino acids to form protein molecules is only one small requirement for life. Most animals are constructed of millions of cells, and the cell itself is far more complicated than the most complex machine ever manufactured by humans.

The famous illustration “the probability of life originating from accident is comparable to the probability of the unabridged dictionary resulting from an explosion in a print shop” argues that information and complex systems cannot come about by chance, but can only be the product of an intelligent designer. Books likewise do not come about by chance, but are the product of both reasoning and intelligence (although some books may cause us to wonder about the author, but this is another problem!). Even Darwin admitted in his writings that it was extremely difficult, or impossible, to conceive that this immense and wonderful universe, including humans with our capacity of looking far backward and far into the future, was the result of blind chance.

Fact Sheet: DNA-RNA-Protein

At their core, all organisms on the planet have very similar mechanisms by which they handle their genetic information and use it to create the building blocks of a cell. Organisms store information as DNA, release or carry information as RNA, and transform information into the proteins that perform most of the functions of cells (for example, some proteins also access and operate the DNA library). This “central dogma” of molecular biology is an extremely simplistic model, but useful for following the flow of information in biological systems. Among the core features:

1. DNA is the genetic material of all cellular organisms.

Deoxyribonucleic acid (DNA) is the material substance of inheritance. All cellular organisms use DNA to encode and store their genetic information. DNA is a chemical compound that resembles a long chain, with the links in the chain made up of individual chemical units called nucleotides. The nucleotides themselves have three components: a sugar (deoxyribose), phosphate, and a nucleobase (frequently just called a base).

The bases come in four chemical forms known as adenine, cytosine, guanine, and thymine, which are frequently simply abbreviated as A, C, G and T. The order, or “sequence”, of bases encodes the information in DNA.

All living organisms store DNA in a safe, stable, duplex form: the famous “double helix”, in which two chains (also known as strands) of DNA wrap around each other. The two DNA strands are arranged with the bases from one lining up with the bases of the other. The sugar and phosphate components run up the outside like curving rails, with the matched bases forming ladder-like rails in the center. (Note – some viruses have their genetic material in the form of a single strand of DNA).

The shape and charge of the bases cause A to bond weakly to T, and C to bond weakly to G. The bases from one strand of a DNA helix are in essence a mirror image of the bases in the other strand – when there is an A in one strand there is a T in the other when there is a C in one strand there is a G in the other. These “base pairing” rules are the key to understanding how DNA carries information and is copied into a new DNA strand (a cell must copy its DNA before it divides into two cells). When organisms copy their genomes, enzymes separate the two strands of the double helix, pulling apart the paired bases. Other enzymes start new DNA strands, using the base pairing rules to make a new mirror image of each of the original strands. Mistakes in this process can lead to mutations (changes in the genomic sequence between generations). Many organisms possess error checking mechanisms that scan through the newly replicated DNA for mistakes and correct them, thus greatly limiting the number of mutations that arise due to replication errors.

2. RNA ”carries” information
DNA holds information, but it generally does not actively apply that information. DNA does not make things. To extract the information and get it to the location of cellular machinery that can carry out its instructions (usually the blueprints for a protein, as we will see below) the DNA code is “transcribed” into a corresponding sequence in a “carrier” molecule called ribonucleic acid, or RNA. The portions of DNA that are transcribed into RNA are called “genes”.

DNA is transcribed to RNA

RNA is very similar to DNA. It resembles a long chain, with the links in the chain made up of individual nucleotides. The nucleotides in RNA, as in DNA, are made up of three components – a sugar, phosphate, and a base. The sugar in RNA is ribose instead of the more stable dexoyribose in DNA, which helps to make RNA both more flexible and less durable.

As in DNA, in RNA the bases come in four chemical forms, and the information in RNA is encoded in the sequence in which these bases are arranged. As in DNA, in RNA one finds adenine (A), cytosine (C), and guanine (G). However, in RNA uracil (abbreviated U) takes the place of thymine (T) (the switch allows RNA some special properties that we won’t go into here, at the cost of making it less stable than DNA). Cells make RNA messages in a process similar to the replication of DNA. The DNA strands are pulled apart in the location of the gene to be transcribed, and enzymes create the messenger RNA from the sequence of DNA bases using the base pairing rules.

3. RNA molecules made in a cell are used in a variety of ways.

For our purposes here, there are three key types of RNA: messenger RNA, ribosomal RNA, and transfer RNA. Messenger RNA (mRNA) carries the instructions for making proteins. Like DNA, proteins are polymers: long chains assembled from prefab molecular units, which, in the case of proteins, are amino acids. A large molecular machine* called the ribosome translates the mRNA code and assembles the proteins. Ribosomes read the message in mRNA in three letter “words” called codons, which translate to specific amino acids, or an instruction to stop making the protein. Each possible three letter arrangement of A,C,U,G (e.g., AAA, AAU, GGC, etc) is a specific instruction, and the correspondence of these instructions and the amino acids is known as the “genetic code.” Though exceptions to or variations on the code exist, the standard genetic code holds true in most organisms.

Ribosomes are found in all cellular organisms and they are incredibly similar in their structure and function across all of life. In fact, the extreme similarity of ribosomes across all of life is one of the lines of evidence that all life on the planet is descended from a common ancestor.

*Biologists often refer to proteins, especially large complexes of proteins, that move, turn, lever, or generally use energy to perform work, as “machines”. Biologists do not mean to imply that such molecules are designed. “Machine” is a useful metaphor for such functions, and simpler and more illuminating than “complex of large molecules that translates chemically stored energy into moving parts”.

4. Ribosomes make proteins using ribosomal RNA (rRNA).
The ribosome reads the instructions found in the messenger RNA molecules in a cell and builds proteins from these mRNAs by chemically linking together amino acids (these are the building blocks of proteins) in the order defined by the mRNA. Messenger RNA molecules are longer than the encoded protein sequence instructions, and include instructions to the ribosome to “start” and “stop” building the protein. Within any particular organism, there can be hundreds to thousands to tens of thousands of distinct mRNAs that lead to distinct proteins. The diversity of form and function in organisms is determined in a large part by the types of proteins made as well as the regulation of where and when these proteins are made.

The ribosome that converts mRNA into proteins is large and complex. It has more than fifty proteins (the exact number varies by species) in two major subunits (known generally as the large and small subunit). In addition to proteins, each subunit includes special RNA molecules, known as ribosomal RNAs (rRNA) because they function in the ribosome. They do not carry instructions for making a specific protein (i.e., they are not messenger RNAs) but instead are an integral part of the ribosome machinery that is used to make proteins from mRNAs. For more information on ribosomal RNA, see here. For information on how we use ribosomal RNA sequences in evolutionary studies, and environmental sampling go here.

Ribosomes do not read the instructions present in mRNA directly – they need help from yet another type of RNA in cells. Transfer RNAs (tRNA) couple amino acids to their RNA codes. Each codon is supposed to be converted into either a specific amino acid in a protein or a specific instruction to the ribosome (e.g., start, stop, pause, etc). At one end, a transfer RNA presents a three-base codon. At the other, it grasps the corresponding amino acid. Transfer RNAs “read”, or “translate”, the messenger RNA through base pairing, the chemical attraction of A for T and C for G, just as the RNA sequence is “transcribed” from DNA by base pairing. The ribosome acts like a giant clamp, holding all of the players in position, and facilitating both the pairing of bases between the messenger and transfer RNAs, and the chemical bonding between the amino acids. The making of proteins by reading instructions in mRNA is generally known as “translation.”

mRNA is translated into protein

This document was produced by microBEnet. It was written by Jonathan Eisen and edited by David Coil and Elizabeth Lester with feedback from Hal Levin.

Why DNA Damage?

They exist in these less stable tautomeric forms only for very short periods of time. However, if a base existed in its rare form at the moment that it was being replicated or being incorporated into a nascent DNA chain, a mutation might result in adenine-cytosine and guanine-thymine base pairs.

The net effect of such an event and the subsequent replication required to segregate the ‘mismatched’ is an AT or GC or AT base pair substitution.

Mutations resulting from tautomeric shifts in the bases of DNA involve the replacement of purine and the replacement of pyrimidine in the complementary strand with the other pyrimidine. Such base-pair substitutions are called ‘Transitions’.

Base pair substitutions involving the substitution of a purine for pyrimidine and vice versa are called transversions. These are possible eight different transversions.

The third type of point mutation involves the addition or deletion of one or a few base pairs. Base pair additions and deletions are collectively referred to as frameshift mutations because they alter the reading frame of all base pair triplets (specifying codons in mRNA and amino acids in the polypeptide gene product) in the gene detail to the mutation.

Suppose three residues or some multiple of three are added or subtracted the remaining residues will still be in the correct triplet sequence for coding the intended amino acids through mRNA transcription. Therefore, the result will be the formation of a peptide chain that has some amino acids missing or additional ones inserted.

If on the other hand, an error in replication changes one or two or some multiple not divisible by three, then the genetic code gets scrambled, and the wrong amino acid will be incorporated into the resultant polypeptide chain at nearly every position.

All the three above-described types of point mutations transitions, transversions, and frameshift mutations are present among spontaneously occurring mutations. A surprisingly large proportion of the spontaneous mutations studied in prokaryotes are found to be single base-pair additions and deletions rather than base-pair substitutions.

Different fundamental forces

All the life forms described above, based on carbon or silicon, in water or in ammonia, crystalline or gaseous, base their physiology on electromagnetic interactions: cells communicate through the flow of ions (electrically charged particles) they are composed by atoms, which are bound to each other by electrical attraction energy is stored, in chemical form, in these bonds.

Electromagnetism is one of the four fundamental forces or interactions, together with gravity, the strong nuclear force and the weak nuclear force. If we define life in the broadest sense - an entity that processes energy to mantain its structure and copy itself - one can conceive very different sorts of life based on different physical interactions.

Electromagnetic life

All chemistry can be described as a system of electromagnetic interactions, but properly electrical and magnetic phenomena are not unknown in familiar life: for example, electroception and electrical synapses. Hoyle's "black cloud" described above lacks true chemistry, but it performs its biological functions by manipulating charged particles with magnetic fields.

Nuclear life

Strong nuclear life

The strong nuclear force, which acts between the particles in the nucleus of an atom, is by far the strongest of all the fundamental forces, and it acts on extremely small and fast scale. It's similar to electromagnetism, but rather than two charges (positive and negative) it's based on three "colors" (red, blue and green) with the respective anticolors, carried by quarks it takes all three colors or all three anticolors to make a neutral particle. Different types of quarks are combined into larger particles called hadrons, which are also called mesons when they're made up by a quark and an anti-quark, and baryons when they're made up by three quarks. Protons and neutrons, which form atomic nuclei, are two kinds of baryons. Other particles, gluons, act as carrier of the force, in the same way that electrons and photons are carriers of the electromagnetic force.

There are several kinds of hadrons, and they could take the role of atoms and molecules on a scale millions of times smaller, while gluons would bind them together or move from one to the other, thus carrying energy. On such a scale, masses are so small that they can be significantly altered by the transfer of energy: hypothetical nuclear organisms would store energy converting it directly into mass, creating quarks, which they'd then destroy in order to release it again. Also, the strength of the strong nuclear force doesn't vary at all within a range of 10 -15 m, 25 000 times smaller than a hydrogen atom, but over that distance it stops working altogether: thus, any nuclear "biochemistry" would have to occur within that scale. Hadrons are not as diverse as atoms, but given that most Earth biochemistry uses only a few elements this isn't necessarily a problem.

The best known nuclear organisms are the cheela from Robert Forward's Dragon's Egg (1980): they live on the surface of a neutron star, 20 km wide, composed by compressed iron nuclei and free neutrons, with mountains a few cm tall. The cheela are 5 mm long and only 0.5 mm high their body, composed entirely by atomic nuclei, is so flattened because of the star's strong gravity. Since nuclear reactions are so much faster than chemical reactions, their metabolism and perception is also much faster: the lifespan of a cheela is about 40 minutes. They appear just 5000 years after the origin of life on the neutron star, and their entire civilization develops in a few days.

Weak nuclear life

The weak nuclear force is, obviously, weaker than the strong one, and it works only in a range a hundred times smaller. It's also far less likely than it, and than electromagnetism, to produce biological systems, as it's the only fundamental force that can't hold matter together. It works through the exchange of W and Z bosons between fermions, a class of particles that includes quarks, electrons, and neutrinos it's involved in phenomena such as radioactive decay and nuclear fusion.

Gravitational life

Gravity is by far the weakest of all the fundamental forces, and it's not much more promising than weak nuclear force, as it's based only on mass, which can never be negative, and therefore it can only attract and not repel. Hoyle's "black cloud" is held together by gravity because of its sheer size, but all its physiology is of an electromagnetic nature. Hypothetical gravitational life would probably be extremely large, with very slow processes, and it would absorb energy by the gravity field of stars and planets, benefiting from the abundance and high efficiency of this form of energy conversion.

Silicon-Based Life May Be More Than Just Science Fiction

Science fiction has long imagined alien worlds inhabited by silicon-based life, such as the rock-eating Horta from the original Star Trek series. Now, scientists have for the first time shown that nature can evolve to incorporate silicon into carbon-based molecules, the building blocks of life on Earth.

As for the implications these findings might have for alien chemistry on distant worlds, "my feeling is that if a human being can coax life to build bonds between silicon and carbon, nature can do it too," said the study's senior author Frances Arnold, a chemical engineer at the California Institute of Technology in Pasadena. The scientists detailed their findings recently in the journal Science.

Carbon is the backbone of every known biological molecule. Life on Earth is based on carbon, likely because each carbon atom can form bonds with up to four other atoms simultaneously. This quality makes carbon well-suited to form the long chains of molecules that serve as the basis for life as we know it, such as proteins and DNA.

Still, researchers have long speculated that alien life could have a completely different chemical basis than life on Earth. For example, instead of relying on water as the solvent in which biological molecules operate, perhaps aliens might depend on ammonia or methane. And instead of relying on carbon to create the molecules of life, perhaps aliens could use silicon.

Carbon and silicon are chemically very similar in that silicon atoms can also each form bonds with up to four other atoms simultaneously. Moreover, silicon is one of the most common elements in the universe. For example, silicon makes up almost 30 percent of the mass of the Earth's crust and is roughly 150 times more abundant than carbon in the Earth's crust.

"My feeling is that if a human being can coax life to build bonds between silicon and carbon, nature can do it too."

Scientists have long known that life on Earth is capable of chemically manipulating silicon. For instance, microscopic particles of silicon dioxide called phytoliths can be found in grasses and other plants, and photosynthetic algae known as diatoms incorporate silicon dioxide into their skeletons. However, there are no known natural instances of life on Earth combining silicon and carbon together into molecules.

Still, chemists have artificially synthesized molecules comprised of both silicon and carbon. These organo-silicon compounds are found in a wide range of products, including pharmaceuticals, sealants, caulks, adhesives, paints, herbicides, fungicides, and computer and television screens. Now, scientists have discovered a way to coax biology to chemically bond carbon and silicon together.

"We wanted to see if we could use what biology already does to expand into whole new areas of chemistry that nature has not yet explored," Arnold said.

The researchers steered microbes into creating molecules never before seen in nature through a strategy known as 'directed evolution,' which Arnold pioneered in the early 1990s. Just as farmers have long modified crops and livestock by breeding generations of organisms for the traits they want to appear, so too have scientists bred microbes to create the molecules they desire. Scientists have used directed evolutionary strategies for years to create household goods such as detergents and to develop environmentally-friendly ways to make pharmaceuticals, fuels and other industrial products. (Conventional chemical manufacturing processes can require toxic chemicals in contrast, directed evolutionary strategies use living organisms to create molecules and generally avoid chemistry that would prove harmful to life.)

Arnold and her team — synthetic organic chemist Jennifer Kan, bioengineer Russell Lewis, and chemist Kai Chen — focused on enzymes, the proteins that catalyze or accelerate chemical reactions. Their aim was to create enzymes that could generate organo-silicon compounds.

"My laboratory uses evolution to design new enzymes," Arnold said. "No one really knows how to design them — they are tremendously complicated. But we are learning how to use evolution to make new ones, just as nature does."

First, the researchers started with enzymes they suspected could, in principle, chemically manipulate silicon. Next, they mutated the DNA blueprints of these proteins in more or less random ways and tested the resulting enzymes for the desired trait. The enzymes that performed best were mutated again, and the process was repeated until the scientists reached the results they wanted.

Arnold and her colleagues started with enzymes known as heme proteins, which all have iron at their hearts and are capable of catalyzing a wide variety of reactions. The most widely recognized heme protein is likely hemoglobin, the red pigment that helps blood carry oxygen.

After testing a variety of heme proteins, the scientists concentrated on one from Rhodothermus marinus, a bacterium from hot springs in Iceland. The heme protein in question, known as cytochrome c, normally shuttles electrons to other proteins in the microbe, but Arnold and her colleagues found that it could also generate low levels of organo-silicon compounds.

After analyzing cytochrome c's structure, the researchers suspected that only a few mutations might greatly enhance the enzyme's catalytic activity. Indeed, only three rounds of mutations were enough to turn this protein into a catalyst that could generate carbon-silicon bonds more than 15 times more efficiently than the best synthetic techniques currently available. The mutant enzyme could generate at least 20 different organo-silicon compounds, 19 of which were new to science, Arnold said. It remains unknown what applications people might be able to find for these new compounds.

"The biggest surprise from this work is how easy it was to get new functions out of biology, new functions perhaps never selected for in the natural world that are still useful to human beings," Arnold said. "The biological world always seems poised to innovate."

In addition to showing that the mutant enzyme could self-generate organo-silicon compounds in a test tube, the scientists also showed that E. coli bacteria, genetically engineered to produce the mutant enzyme within themselves, could also create organo-silicon compounds. This result raises the possibility that microbes somewhere could have naturally evolved the ability to create these molecules.

"In the universe of possibilities that exist for life, we've shown that it is a very easy possibility for life as we know it to include silicon in organic molecules," Arnold said. "And once you can do it somewhere in the universe, it's probably being done."

It remains an open question why life on Earth is based on carbon when silicon is more prevalent in Earth's crust. Previous research suggests that compared to carbon, silicon can form chemical bonds with fewer kinds of atoms, and it often forms less complex kinds of molecular structures with the atoms that it can interact with. By giving life the ability to create organo-silicon compounds, future research can test why life here or elsewhere may or may not have evolved to incorporate silicon into biological molecules.

"In the universe of possibilities that exist for life, we've shown that it is a very easy possibility for life as we know it to include silicon in organic molecules. And once you can do it somewhere in the universe, it's probably being done."

In addition to the astrobiology implications, the researchers noted that their work suggests biological processes could generate organo-silicon compounds in ways that are more environmentally friendly and potentially much less expensive than existing methods of synthesizing these molecules. For example, current techniques for creating organo-silicon compounds often require precious metals and toxic solvents.

The mutant enzyme also makes fewer unwanted byproducts. In contrast, existing techniques typically require extra steps to remove undesirable byproducts, adding to the cost of making these molecules.

"I'm talking to several chemical companies right now about potential applications for our work," Arnold said. "These compounds are hard to make synthetically, so a clean biological route to produce these compounds is very attractive."

Future research can explore what advantages and disadvantages the ability to create organo-silicon compounds might have for organisms. "By giving this capability to an organism, we might see if there is, or is not, a reason why we don't stumble across it in the natural world," Arnold said.

The research was funded by the National Science Foundation, the Caltech Innovation Initiative program, and the Jacobs Institute for Molecular Engineering for Medicine at Caltech.