Review: The Philosophy of Transhumanism by Max More

Review Introduction

This is the first in what will be a series of reviews of the essays written by various authors over a number of years, collected by Max and Natasha Vita More in “The Transhumanist Reader” (link to purchase at bottom). It is intended to expose the reader to some key, high-level ideals coming from individuals who associate themselves as transhuman, the belief that  we can and should improve the human organism beyond natural limitations through the use of science and technology.

In his essay; The Philosophy of Transhumanism, Max More explores the concept of transhumanism and its growth as a philosophy and movement from a number of current and historical perspectives. I’ve picked out a few highlights while leaving much for the reader to explore.

The Philosophy

To the author, transhumanism has a distinct identity harnessed from different definitions and sources from the topic of philosophy. It bares open different themes, interests and values that make transhumanism what it is, which according to the author is “Philosophies of life…that seek the continuation and acceleration of the evolution of intelligent life beyond its currently human form.”

To him transhumanism ranks alongside Confucianism and secular humanism, both worldviews that practically impact our very lives without the use of superstition or (physically) transcendent beliefs. A philosophy that- contrary to religion and superstition, emphasizes a transformation inspired by reason and science.

Max More believes that the transhumanist reliance on technology to eliminate biological limits as opposed to education and cultural improvements means that risks and costs can be kept at a minimum while shaping our nature for deliberate results. We would no longer be human but rather, posthuman since we would no longer suffer aging or even death, although other challenges might surface at the time.

Posthumans would have free form and cognitive capabilities as well as better emotions (e.g less sorrow and more joy) refined and controlled by the posthuman and if transhumanists have their wishes, then there will also be a much larger environment to live in, not the least being space itself and newly created and rich virtual worlds.

Furthermore, the author maintains that understanding the potentials of transhumanism requires the integration of physical and social sciences such as was developed from the principles of “extropy,” first published in 1990 and that the value of independent thinking gives way to rationale whose advantages would be the ability to reason rather than be blinded to faith and in the end learning by experiment instead of believing. In the end however, he also suggests that emphasis on “transhuman-ism” over “trans-humanism” might cause transhumanists to reject the concept of open society even as it is thus far very compatible with their goals of continual improvement instead of a utopia.

He also states that some transhumanists have attempted to avoid cognitive biases as well as deficient cognitive shortcuts yet the philosophy requires extensive and critical thinking and analysis. Nevertheless, the epistemological (a branch of philosophy that investigates the origin, nature, methods, and limits of human knowledge) views of transhumanists range widely, where some thinkers support the concept of foundationalism such as was Descarte’s insistence that God was at the center of the foundations of knowledge. Idealists and empiricists- More continues- concentrate more on seeking unquestionable or self-evident signs of intellectual intuition while eliminating the idea of God, a view which is itself challenged by critical thinkers who insist that reasoning must be used systematically even while giving up justification.

Critical rationalism then would appear to be a close fit for transhumanism, but then, there also exists another group of transhumanists, inspired by Ayn Rand and remain committed to a foundationalist epistemology where knowledge is hierarchical and based upon undeniable axioms. To More, some critics confuse functionalism with dualism not paying attention to the fact that the cognitive system or mental state is not dependent upon the physical instantiation and he blames this to the theory that these critics have read too much mind “uploading” literature.

Max More also introduces us to Eliminativism, which argues against the concept of common sense and that some mental states are non-existent in the brain. Furthermore, eliminativism contends that belief, intention or desire don’t have coherent basis of neurology.

Revisionary materialism on the other hand argues that states are reducible to the state of physical phenomena as soon as changes have been made to the concept of folk psychology. This position excites transhumanists most because it allows the full extent of reconceptualization of the cognitive architecture of humans.

While humans have lived in an entirely physical universe, More suggests a time when we would actually spend considerable time in simulated environments. In fact, there are those who have questioned if we aren’t already living in a simulated environment! He goes on to suggest that transhumanism may actually be able to co-exist with religion, being a form of life without a reference to a higher power and even says that some transhumanists already hold religious beliefs anyway, most of whom seem to be Mormons (perhaps owing to their teachings that humans can ascend to god-like status) while Christian transhumanists are rare.

All in all, in the article’s section on Philosophy, Mr More takes us on a compelling a thought-provoking journey via comparative analysis to give us a view of some of the philosophical variances that exist thought the communities that identify as transhumanist. It is an enjoyable ride.

History

Max More, in his essay takes the time to run us through the history of transhumanism, from early definitions such as Dante Alighieri’s divine comedy of 1312 to Julian Huxley’s “New bottles for New wine” a 1957 book in which he included an entire chapter called “Transhumanism.”

More however emphasizes that the history of the philosophy that transhumanism became is varied and depends largely on different sources. There are precursors and proto-transhumanists between the thirteenth and eighteenth centuries who searched the Elixir of life and philosopher’s stone. One such person was Pico della Mirandola whose 1486 essay “Oration on the dignity of man” has lately made him a subject of much controversy owing to his insistence that God is the craftsman. Some transhumanists today take offence at his refusal to give humans some credit especially as regards their ability to recreate themselves even as his essay suggests that God gave man the freedom to choose his form.

Darwin’s “Origin of species” 1859 was the one that ultimately released the possibility that humans could just be getting started in their evolutionary path and led to scientists such as Friedrich Nietzsche to suggest that “humans can be overcome” and used such boldness that transhumanists were inspired to follow through on his challenge to “overcome” humans.

Later precursors such as Nikolai Fedorovich Fedorov (1829– 1903), a Christian philosopher advocated for scientific methods to achieve immortality and even raise those who died back to life in new, immortal forms since evolution came with increased intelligence. Jean Finot, who came shortly after Fedorov went as far as to suggest the use of science to engineer life.

Mr More goes on to more modern, broader-thinking influences and notable introductions such as cryonics and the prospect of immortality, the role of the arts and Natasha Vita-More’s 1982 Transhuman Manifesto, the Extropy Institute, the 1998 Transhuman Declaration, and the on-line Vital Summit in 2004 birthing the Proactionary Principle.

Currents

Max More discusses current trends, or rather demonstrates a range of perspectives on transhumanism while acknowledging the unifying theme that to overcome biological limitations is as possible as it is desirable.  Likewise, they tend to favour the route of personal choice, such as cryonics, mood modifiers, and more freedoms of form.  Some transhumanists would favour, or at least predect a “singularity,” a kind of single government likely headed by one supercomputer.

He discusses in some detail the reasons for varying views on the subject and acknowledges that there are those that are wary of even the attempts to move toward a transhuman existence.

And there are risks.  More includes them in his essay while stating that since the early days of transhumanist discussions, risks were put into consideration thanks especially to the efforts of “bioconservatists” and other transhumanism opponents who continued to highlight them and insist on cultural consensus. Consequently, the likelihood of the extinction of the human race has been – and continues to be – explored. Some transhumanists have argued that extinction is inevitable (i.e. via catastrophes and pathogens) unless transhumanism is widely adopted and implemented.

Misconceptions

Finally, Max More takes the time to explain transhumanism by actually responding to various misconceptions about it.  These include critics who see the association as wide-eyed utopians, as people who claim to be predicting the future, and that transhumanists intensely dislike their bodies and are afraid of death. He counters each eloquently in turn indicating the principle of continuous improvement rather than any state of perfect stasis, transhumanist’s developing expectations along the lines of obvious technological advance (with no particular timelines, counter to ‘prediction’), the admiration of the human organism and the desire to improve upon it, and to counter the final criticism, that of thanatophobia, More cites the desire to maintain the continuity of existence rather than flee the unknown of death.

This is a great section of the essay that helps wrap things up by framing some of the philosophical underpinnings, in relatively concrete terms.

Review Conclusion

In conclusion of this review of Mr More’s essay, it is a terrific start to what I am now more than ever convinced will be a fantastic foray into the philosophies and perspectives generated by those with a common belief that we can and should improve the human organism.  I recommend getting your own copy of The Transhumanist Reader.

AMAZON: The Transhumanist Reader: Classical and Contemporary Essays on the Science, Technology, and Philosophy of the Human Future

All quotes and examples are taken from “The Philosophy of Transhumanism,” Max More, as printed in the Transhumanist Reader (link above).

The Future Human Evolution Website does not gain financially from providing reviews of any future-related literature/media, nor do the views expressed in such media necessarily reflect the views of its writers, editors, and publishers.

 

Transhuman, Post Human, and Human Plus (+)

Introduction

When an idea’s time has come, it has come. It is the confluence of all of mankind’s known history and knowledge of the many divergent paths of progress all around us. The more varied and independently the idea emerges across media, cultures, disciplines, and genres, the more it is representative of natural human progress. Tranhumanism, in its simplest form, is such an idea.

Transhuman & Post Human vs. Transhumanism and Human Plus

To forgo for a moment all of the various philosophies and riders and amendments that have been attached to the notion of a transhuman over the years and to spell it out in plain English, the most basic definition of a transhuman is a person who has used or is an advocate of using, technology to improve the human mind and body. In the history of its terminology the “trans” prefix refers to a supposed human body transitory growth and change period on the way to a predicted condition in which the human organism becomes so far advanced relative to the present day human in mental and physical capability, that it would be “post” human. One no longer needs to hold true the “goal” or idea of a post human existence in order to embrace the transhuman condition. Perpetual change and betterment may forever have us in a transitory state.

In the world of the internet “transhuman” appears to be most often associated with “transhumanism” which by typical meaning encompasses several schools of thought, some of which have associated organizations that promote a particular creed.  Human+ (or plus) is a relatively recent euphemism for transhumanism and the name of an international organization that promotes a particular variety of transhumanism.

To Join or not to Join

An important point here is that one does not have to be a member of an organization to possess transhuman ideals; that is, to simply believe that technology can and should be used to improve the human body and condition.  One need not have “learned” the notion of applying technology to make a better human from any transhuman organization, member, or publication. You may have observed the world and come to that conclusion independently even decades ago, been influenced by the plethora of visionary science fiction writers since the golden age, and/or have been encouraged by the tremendous scientific and technical progress of today. Whatever your path to enlightenment, please feel free to possess the belief that technology can improve us, without your needing to adopt, create, or carry any specific doctrine or philosophy.

Having made that point, here’s another equally important: certainly one may join a transhumanist organization as one would for any special interest: to congregate, socialize, and develop relations with others of similar interest or even passion, to partake of the many interesting thoughts and writings on transhuman ideals, and/or to contribute your own thoughts and opinions on message boards, blog comments, or other types of interaction.

The Interesting thing about Transhumanism

The transhumanist movement has attracted a lot of insightful philosophical thinking over the years which in turn has produced some interesting writing on the various aspects of the technologically advanced human organism.  Interesting scenarios, cogitation on social equality, influence on the Arts, and proposed principles for transhumanist’s living have all been put to pen. My interest in this literature was recently rekindled by a newly assembled collection of old and new transhuman essays, called The Transhumanist Reader: Classical and Contemporary Essays on the Science, Technology, and Philosophy of the Human Future. (Links to Amazon for purchase).

Inside this Transhuman Website Section

As I work my way through The Tranhumanist Reader collection as time allows, I thought it might be interesting for the reader here to benefit from the more enlightening or compelling ideas contained in the essays. In this section of the website, at least as initial and convenient fodder for the many perspectives of tranhumanist ideals, I’ll review (not reprint) and comment on select essays from that particular collection and provide a link like the one above in case you would like to purchase and read the collection in full.

The Future Human Evolution Website does not gain financially from providing reviews of any future-related literature/media, nor do the views expressed in such media necessarily reflect the views of its writers, editors, and publishers.

Stay tuned!!!

Visualizing the Universe: Human Vision

We humans have two eyes and not one or three, like much of the hunting animal world because it is the minimum required to have depth perception – the ability to gauge the distance between yourself and your prey.  Vision involves the nearly simultaneous interaction of the two eyes and the brain through a network of neurons, receptors, and other specialized cells.

visualizing-the-future-human-vision

visualizing-the-future-human-vision

The first steps in this sensory process are the stimulation of light receptors in the eyes, conversion of the light stimuli or images into signals, and transmission of electrical signals containing the vision information from each eye to the brain through the optic nerves.

The human eye is equipped with a variety of optical components including the cornea, iris, pupil, aqueous and vitreous humors, a variable-focus lens, and the retina. Together, these elements work to form images of the objects that fall into the field of view for each eye.

When an object is observed, it is first focused through the convex cornea and lens elements, forming an inverted image on the surface of the retina, a multi-layered membrane that contains millions of light-sensitive cells.

In order to reach the retina, light rays focused by the cornea must successively traverse the aqueous humor (in the anterior chamber), the crystalline lens, the gelatinous vitreous body, and the vascular and neuronal layers of the retina before they reach the photosensitive outer segments of the cone and rod cells. These photo sensory cells detect the image and translate it into a series of electrical signals for transmission to the brain. Ironically, despite the fantastic, seemingly evolution-defying complexity of the human eye, it is merely a light collection device. It is the brain that actually “sees” i.e. takes the light and converts it into intelligible information upon which the rest of the brain can act.

The eye being just a collection device and light being just another electromagnetic wave opens up the possibilities of science fiction becoming science fact: soon humans will have the ability to equip ourselves with “Geordie” style visors and ocular implants that enable us to see all of the electromagnetic wave spectrum. In fact scientists are now successfully experimenting with getting mice to “see” infrared light through direct cortical stimulation. See the full Scientific American article here.

Color blindness, a disruption in the normal functioning of human photopic vision, can be caused by host of conditions, including those derived from genetics, biochemistry, physical damage, and diseases. Partial color blindness, a condition where the individual has difficulty discriminating between specific colors, is far more common than total color blindness where only shades of gray are recognized.

 

General Applications of Genetic Engineering

Introduction

Gene cloning has had a massive impact in basic biological research as well as the everyday life of the general public. In this article we will discuss some basic biological research, as well as the areas of therapeutic cloning and gene therapy. We’ll also delve into the topic of Genetic engineering to produce recombinant human proteins, and Genetically modified organisms and the fascinating world of Transgenics.

Basic Biological Research:

basic-biological-research-future-human-evolutionFor any application, scientists require thousands or even millions of copies of the same gene in a test tube. Once this has been achieved, it can be used for various purposes.

When a gene is cloned in a vector, it becomes possible to sequence the gene—the process of finding out the precise order of bases that appear in the gene. This is possible because DNA is made up of four bases: adenine, guanine, thymine and uracil. The sequence of these bases in the DNAdirects the process of transcription–the production of mRNA that in turn dictates the sequence of amino acids in the protein. Thus, gene sequencing is an important part of basic biological research. There are public databases where scientists deposit the sequence of genes once they are sequenced both for public and scientific use. After sequencing, it is possible to know which protein the gene makes.The genetic code is applied to determine the precise order of amino acids in the protein. The sequence of the protein is then compared with all the known proteins (over 50,000) in databases like Swissprot Uniprot and others, which are databases used to house biological information about known proteins for public and research use. Comparisons can be easily done using computers and software that are available in nearly every lab. If the unknown protein is similar to one in the database, it is possible to guess the function of the gene. Even if there are no identical proteins, there are many other ways to guess the function of the gene once it is cloned (1,2,3).

An example of this application is the identification of the gene responsible for cystic fibrosis. This gene was identified in 1989 when it was cloned and the protein it coded was found to be responsible for calcium transport in lung cells. If this protein is defective, calcium transport is deficient and mucus accumulates in the lungs leading to cystic fibrosis. Once the gene responsible for disease is known, it is possible to begin experiments aimed at discovering a cure. There are many other diseases which are caused by a defect in a single gene, and genetic engineering has made it possible to identify them(4).

Therapeutic cloning:

Therapeutic cloning is a process in which nuclear material is transferred (nucleus) from an individual into an enucleated egg (an egg whose nucleus is removed) to derive embryonic cells with the same genome as the nuclear donor. Once the embryonic cells are formed, they are grown to stem cells. These stem cells can now be used to grow replacement organs like heart, lungs and so on by a process called organogenesis. And since the genetic material of the organ is derived from the donor, the problem of immune rejection is circumvented. In fact, laboratory studies show that this method holds immense promise in the treatment of diseases like Parkinson’s disease, Duchenne Nuscular Dystrophy and Diabetes Mellitus. Moreover, combined with gene therapy, therapeutic cloning could be used in treatment of many other genetic diseases. The basic steps for therapeutic cloning arestraightforward: first,DNA is extracted from a sick person. It is then inserted into an enucleated donor egg, causing the egg to divide, similar to a fertilized egg. This forms an embryo, the place where stem cells are collected. Finally these stem cells may be used or grown to any kind of tissue or organ for treatment of the patient. However, many technical and non-technical (legal, ethical, political and economic) concerns that must be addressed before therapeutic cloning can live up to its expectation (5,6,7).

Gene therapy:

When a person falls ill, it is often due to an invading microbe which damages or destroys cells and organs in the body. Diseases like cholera, AIDS, diphtheria, measles, and the common cold are a few examples of this type of illness. These types of diseases are called infectious diseases. When a person suffers from a infectious disease, the physician prescribes a drug which fights the microbe and often removes the microbe, thus curing the sick person. However, most of the diseases people suffer from are not of this type. The diseases that are caused by alterations in genes are termed genetic diseases. These diseases may arise due to one or more mutations in a normal gene that eventually lead to a nonfunctional protein or no production expression at all. Thus, the biochemical pathways that the protein is involved in are disturbed, and the disturbance manifests itself as genetic disorder. There are several thousands of genetic diseases that cause serious threats worldwide, such as cancer and cystic fibrosis.

Gene therapy is a simple approach to cure genetic diseases. If a disease is caused by a faulty gene, it must be possible to cure the disease by repairing the gene. Many approaches can be used to achieve this goal. The most common approaches are to add a normal version of the gene or cells that express the normal version of the gene to the patient’s body.. Although gene therapy is simple and straightforward in theory, there are numerous technical problems that can arise when trying to repair the faulty gene. Identifying the faulty gene, delivery of the normal gene, controlling gene expression, and duration of gene action are among the main technical problems that still need to be addressed for gene therapy to become the forerunner of treatment of genetic disorders (8).

Genetic engineering to produce recombinant human proteins

As we know, proteins are the real “workers” in the cell. Proteins are required for structural integrity, function, regulation and survival of tissues and organs. Without protein there can be no cell, and without cell there can be no life. Proteins can act as antibodies, which recognize and destroy invading pathogens like bacteria and viruses, thus helping to protect the body. They are enzymes that carry out all the biochemical reactions happening inside the body. They are also indispensable for maintenance and flow of the genetic code. They act as messengers (e.g. hormones) to transmit signals between different cells, tissues and organs. Proteins that provide structural integrity to organs help us to move. Proteins also transport molecules throughout the body per the body’s needs.

Given the immense importance and versatility in function of proteins it is easy to imagine that they are widely used in research, medicine, and industry. But the extraction of proteins from the natural source is an extremely delicate, difficult and expensive process. Genetic engineering provides an alternative to this problem by making it possible to transfer the gene that codes for a particular protein and express it in either a prokaryotic or eukaryotic host. This is done by putting the gene of interest in a vector with promoters, enhancers and other sequences required for the expression of the gene in host cells. The vector is then introduced into hosts like bacteria, yeast or mammalian cells that produce a large amount of protein (9). The applications of recombinant proteins is vast. Recombinant proteins can be used in protein replacement therapy if aberration in a protein is identified as the cause of a genetic disease, and the recombinant protein can be used for its treatment. Insulin was the first protein  produced by genetic engineering, and the recombinant insulin can used for the treatment of diabetes mellitus (10,11,12). Dwarfism is also a genetic disorder–it is caused by the underproduction of human growth hormone in the body. The synthetic human growth hormone can make up for the body’s deficiency of the hormone (13). Similarly, bacteria-derived interferon was shown to reduce symptoms of hepatitis, decrease the spread of herpes zoster, and shrink certain tumors (14). Many other recombinant proteins have been expressed and patented by companies. Some of the examples include: Erythropoietin (a protein that controls the formation of red blood cells) patented by Amgen (15,16), Tissue plaminogen activator (protein responsible for breakdown of blot clot) patented by Genentech (17,18), and Aldurazyme (enzyme that degenerates glycosaminoglycans in lysisimes) by BioMarin Pharmaceutical and Genzyme (19,20).

Genetically modified organisms/ The Fascinating World of Transgenics

Genetically modified organisms (GMOs) are organisms whose genetic makeup has been altered in such a way that it would not occur naturally (through mating and/or natural recombination). Genetic engineering provides an option to transfer a selected gene or genes from one organism to another. The gene that is inserted into a foreign organism is called a “transgene” and the organism made during the genetic modification process is called “transgenic.”There are several approaches that can be used to make a transgenic organism. In the first, the desired transgene is identified and cloned. Then it needs to be inserted into the target organism. To make transgenic animals, the desired gene is micro-injected into the reproductive cell of the organism, the cell is grown in vitro (in the lab) to embryonic stage, and then inserted into a centerpiece female where it is nurtured and a modified organism is born. Another approach is to use retroviruses that have been crippled so that they cannot cause infection, but carry the transgene and inject it directly into the host cell where the transgene incorporates in the host genome. The third approach is to use totipotent stem cells, which are cells that can grow into any cell (like liver cells, neuronal cells and so on). In this approach, totipotent stem cells are isolated from the host’s embryo, injected with the desired transgene, and reinserted into the host embryo. This embryo is then grown to a genetically altered adult (21). Unlike animals, all of the cells in plants retain the capacity to develop into a new plant, thus the transgene maybe inserted by any of the transfer methods into a single cell. Tissue culturing is then done to propagate the cell such that multiple cells express the transgene, and the development of transgenic plant is possible. Once the plant is made, nature increases the plant number through normal seed production and propagation (22).

Transgenics has a widespread application. Given the population explosion over the last 100 years, coupled with the decreased availability of land for farming has led to a high demand for food. At present, crop yields are barely keeping up with demand. Genetic engineering of plants has the potential to overcome this problem through the sustainable and safe production of food with increased nutritive value, better flavor, prolonged freshness and even disease fighting abilities. Moreover, it is possible to make crops with higher yields which are naturally resistant to insects and pests. This particular ability of genetic engineering helps to protect the soil by decreasing or entirely removing the need for insecticides, pesticides, herbicides and fertilizers. There are numerous examples of GM crops with better qualities. Fruits have been produced which ripen on the vine for better taste yet have a longer self life. Today, genetically engineered bacteria is used to produce an enzyme called chymosin that is used to produce most  cheese products. Increasing the level of iron in rice is a potential remedy to combat the problem of iron deficiency that affects over two billion people worldwide.. A company called Monsanto found a way to increase the starch content of a potato, which has the advantage of reduced oil absorption during frying, thus lowering the cost of French fries, chips, and so on, while  at the same time reducing the fat content. In addition, since the production of is, Scientists are also trying to produce edible vaccines in tomatoes and potatoes to help with the issue of a tiresome, long and expensive process to produce medicines and vaccines (23).

Similarly, transgenic animals have a widespread application in agriculture, medicine, and industry research.. Selective breeding to produce animals exhibiting desired traits like increased milk production and higher growth rates has been practiced. However, selective breeding is difficult and time consuming. Genetic engineering solves these problems by using tools that make it possible to develop the desired traits in animals in a relatively short time and with more precision. For example,transgenic cows that produce more milk or milk with less cholesterol or less lactose; Sheep that can grow more wool;pigs and cattle that produce more meat are already available (24). Moreover, scientists are working on making disease resistant animals like cows resistant to intramammary Stephylococcus aureus (25). Transgenic pigs may be used to produce transplant organs like hearts, livers, and kidneys. This process is called xenotransplantation. However, there is still a problem of organ rejection that needs to be addressed (26). Transgenic animals may also be used as “bioreactors” to produce important and valuable human proteins, enzymes, hormones and growth factors. This method is a cost effective alternative to cell culture method discussed above (27). Various research has been done to explore the possibility of production of growth hormones, anti-clotting factors, and insulin from the milk of transgenic animals. In particular, scientists are working on producing milk for the treatment of diseases like phenylketonuria, cystic fibrosis, and hereditary emphysema (28). Perhaps the best example of industrial application of transgenic animals is the production of “Biosteel” from transgenic goats. Nexia, a Canadian biotech company has produced trangenic goats that produce spider silk protein that is stronger and more flexible than steel. This silk is so strong that it could be used to make bullet proof vests, and may also have applications in the aerospace industry. Owing to its compatibility with the human body, this silk may further be used to help tissue repair. Transgenic animals can also be used in research to answer fundamental questions in biomedical sciences like gene expression and regulation, developmental biology, immunology, and cancer research, and at the same time they can be used as models for human genetic diseases like muscular dystrophy, and sickle cell anemia among many others (28,29).

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  • Author   Lillico S.G. et al.
  • Title   Transgenic chickens as bioreactors for protein-based drugs
  • Publication   Drug Discovery Today
  • Date   2005
  • Volume/section/page 10(3): 191-196
  • Web addess  http://www.ncbi.nlm.nih.gov/pubmed/15708533

 

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  • Author   Pusta Dana et al.
  • Title   Animal transgenesis and its Applications
  • Publication   Veterinary Medicine
  • Date   2010
  • Volume/section/page 67(1)
  • ISSN   18435270
  • Electronic ISSN 18435378

 

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  • Author   Houdebine LM.
  • Title Use of transgenic animals to improve human health and animal production.
  • Publication  Reprod Domest Anim
  • Date   2005
  • Volume/section/page 40(4): 269-81

Basic Concepts in Genetic Engineering

The “Gene” Unraveled

In this article we’re going to look at a definition of Genetic Engineering, explore the concept of a “gene” and how that understanding has evolved over the past 150 years or so and why it is still not 100% agreed upon by everyone, as well as some fundamental mechanics of genetic engineering like “restriction enzymes”.  Finally we’ll learn how the role of “junk DNA” is becoming more understood as anything but, and we’ll end with a quick look at the Human Genome Project and how that project has provided more information…and questions…on what exactly a “gene” really is.

Inside this Page

  • A Definition of Genetic Engineering
  • Our Evolving Understanding of the Gene and Genetic Engineering
    • Genotype and Phenotype
    • Evolution of the term “Gene”
    • Restriction Enzymes
    • Junk DNA
    • The Human Genome Project

Definition of “Genetic Engineering”

In its very simplest form, genetic engineering can be defined as a technique used for the manipulation of genes. However, a more accurate and broader definition would be that genetic engineering encompasses a number of methodologies which enable new combinations of genetic material to be artificially constructed in a laboratory. If we take a closer look at the simpler defintion, it might seem that genetic engineering is a very old field because humans have been manipulating the genome of organisms using artificial and selective breeding for thousands of years. But the science of entering into a cell and manipulating its genome by adding or removing gene (s) is a very new field which has made remarkable progress in the past few decades.

Genetic engineering as a field of biology is a result of progress in many different fields including molecular biology, evolution, heredity, molecular genetics, engineering and so on. Many discoveries and discoverers have contributed to the development of this particular branch of biology. Some of the major discoveries will be highlighted here.

Evolution of the “Gene” and Genetic Engineering Concept

Genotype and Phenotype

If we take a minute and think about whats around us we will realize that there are two major types of things: living and non-living. Living organisms are made up of about 98% of basic elements which are carbon, hydrogen and oxygen, 1% nitrogen and the rest of 25 different elements. The non-living world (only our planet) is made up of 100 known elements. The biggest difference in living and non-living world is that the combination and composition of elements in the living world happens in such a way which makes a system, capable of growing and most importantly reproducing itself. How this happened is an entirely different field of biology called molecular evolution.

Living things are capable of reproducing themselves but how is it that a dog produces a dog, potato seeds grow into potato plants and humans reproduce to have a baby? The physical traits of a living organism combine to be called its phenotype. The differences in phenotype even withing the same species (whether it be potatos or people) are possible because parents can pass something called genome (entire set of genes) to their offspring. This trait of a living organism is its genetic make up referred to as genotype. Thus, the phenotype of an organism is the result of the expression of its genotype.

1 Basic Concepts in Genetic Engineering genotype-phenotype

This is the reason why there are differences among humans, eye color, height and so on. Each individual have their own set of genotype and thus a different phenotype. By now we can realize that a gene is something that brings a phenotype into being. However, for a phenotype to manifest there are many levels of complexity arising from the interaction of various genes, their expression to form proteins, regulation of expression and so on.

Human Understanding of the Gene

The concept of “gene” has undergone a lot of changes and has become more complex compared to when it was first coined by Wilhelm Johanssen in 1909 (1). Infact, the concept is still changing and there is not a complete and clear conscience of what a “gene” really is among scientists. Johanssen coined the term gene to explain observations made by Gergor Mendel in 1866 during his work with peas. Mendel founded theory of heredity by crossing peas with different traits and studying the traits in successive generations. The factor responsible for transmission of biological traits was called “gene” (2).

2 Basic Concepts in Genetic Engineering gregor mendel

A modern Gregor Mendel T-Shirt.

In 1900, Walter Sutton came up with “Chromosomal theory of heredity” which showed that genes are located in chromosomes. His work was important because it mixed genetics (breeding experiments) with cytology (study of cell structure) (2). Then during the 1910’s gene was found to be a “distinct loucs”. T.H. Morgan came up with a model to show that genes are linearly arranged and the frequency with which the cross-over is proportional to the distance between them (3). The first genetic map was made in 1913 by Sturtevant (4) and in 1915 T.H. Morgan came up with “Mechanism of Mendelian Inheritance” describing the mechanism responsible for what Mendel had discovered and thus vindicating him (3). For geneticists of this time, gene did not have a physical existence, it was something abstract whose existence manifested only as a result of transmission of physical traits. Then in 1941, Beadle and tatum showed that mutation in a gene causes defect in steps of metabolic processes. Thus they came up with “one gene one enyme” hypothesis which was later replaced as “one gene one polypeptide” hypothesis (5). This was a more mechanistic view of gene, it meant that genes are implict information about individual molecules in a metabolic pathway. During the 1950’s it was shown that gene was not something abstract but had a physical existence. This was due to various observations. Muller showed that X-ray could cause mutation (6), Griffith showed that virulent but dead Pneumococcus could be taken up by avirulent living one and get transformed into virulent (7). Avery in 1944 showed that the unit of inheritance or gene could be destroyed by DNAse (any of several enzymes that break down the DNA molecule into its component nucleotides) (8). Finally in 1955, Hershey and Chase proved conclusively that the unit of inheritance was DNA and not protein (9). 1960s was the time when the science of gene and molecular biology sky-rocketed. Watson and Crick cracked the structure of DNA, they showed how a double stranded helical DNA could replicate itself thus solving the structural basis for inheritance (10).

DNA-Double-Helix-Future-Human-Evolution-Website

There was the discovery of messenger RNA which is a transcription product of DNA. The genetic code was discovered which explained how mRNA dictated the sequence of incorporation of amino acids in a chain to form protein. Thus the flow of information from DNA to RNA to protein was clear, this was termed “The Central Dogma” by Francis Crick (11). Gene was now a code that gave rise to a functional product. However, there were many exceptions: it was known that many genes do not make proteins. For e.g. some genes make tRNA, rRNA but these are never translated to make proteins. By now it was clear that gene is a stretch of DNA and it produces a functional product which somehow brings a trait into being.

Restriction Enzymes

The landmark discovery which lead to the foundation of genetic engineering was the discovery of restriction enzymes (restriction endonucleases) by Herbery Boyert and Stanley Cohen in 1973. Restriction enzymes are produced by bacteria and function as a simple immune system. They protect bacteria from possible invasaion of viruses. They recognize a certain sequence in DNA or RNA and chop it. HindII was the first discovered restriction enzyme but thousands were dicovered later. The property which has made restriction enzymes workhorses of molecular biology is that each resriction enzyme recognizes and cuts a specific, short nucleotide sequence not found in the bacteria. Since restriction enzymes can recognize and cleave that particular sequence not only in viruses but any other DNA/RNA containing that sequence, their use was immediately identified. It meant that now it was possible to cut a piece of DNA from one source and possibly ligate the piece into DNA from another source cut with the same enzyme (using enzymes called ligases) (12).

Junk DNA. Not!

Now that it was possible to move a particular gene around, it became easier to study how genes behaved. It was found that over 98% of the genome in humans do not code for proteins,instead they were labelled “junk DNA”. However, it is slowly being discovered that these so called junk DNA are important not only to regulate the level of expression of the genes but also play an important role in evolution, as they contain clues to what direction did evolution take. Similarly, a whole myraid of small RNA molecules were discovered which were termed as non-coding RNA. Examples include: micro RNA, small interfering RNAs and so on. These small RNAs have been shown to be important in regulating gene expression at post-transcriptional level. Similarly, many genetic genetic disorders have been found to correlate with abnormal levels or activities of these small non-coding RNAs.

The Human Genome Project

human genome project Logo and Title Page

Human Genome Project Logo and Title Page

The completion of the Human Genome Project was a landmark in the history of science. However, there was a shock among biologists when it was discovered that the human genome contains only 25-30000 genes but about 100000 proteins. If gene is a stretch of DNA making functional product (protein), how can it be that the number of observed genes are so much less than the number of proteins. This is due to the enormous complexity of the nature of molecular genetics in humans. Phenomenon like splicing, can make two mRNA from the same DNA stretch, thus making 2 different proteins.

One definition of a gene

One definition of a gene

There are so many other processes and structures in the human genome which together help and maintain a homeostasis in the level of gene expression, both spatial and temporal. Although there is no one clear definition that scientists accept, there are a few working definitions which make it easier for scientists to commnunicate without making things complicated (13). A gene was defined by the Human Genome Nomenclature Organization as “a DNA segment that contributes to phenotype/function. In the absence of demonstrated function a gene may be characterized by sequence, transcription or homology” (14). The Sequence Ontology Consortium reportedly called the gene a “locatable region of genomic sequence, corresponding to a unit of inheritance, which is associated with regulatory regions, transcribed regions and/or other functional sequence regions” (15). Although these are widely accepted there are problems with these views of the gene because it is a more “sequence based” view. There are phenomenon like frameshifting, splicing which can produce mutiple protein products. The protein coding sequence of DNA is usually present between non coding ones forming an open reading frame. This causes a problem when genes are defined as “locatable region of genomic sequence”. There are distinct regulatory sequences which are directly involved in transcription e.g. enhancers, silencers but these sequences do not code for any functional product. There are mobile elements in the genome which enable genetic elements to appear in a new location over generations. There are processes of epigenetics which change the phenotype without changing the sequence of DNA and many such mechanisms exist which do not agree totally with the “sequence-based” definition of a gene.

REFERENCES

  • [1] Author  Nils Roll-Hansen
  • Title   The crucial experiment of Wilhelm Johannsen
  • Publication  Biology and Philosophy
  • Date   July 1989
  • Volume/Section/Page Volume 4, Issue 3, pp 303-329
  • Web Address  http://link.springer.com/article/10.1007%2FBF02426630
  • [2] Author   Mark B. Gerstein et al.
  • Title   What is a gene, post-ENCODE? History and updated definition
  • Publication  Genome Res
  • Date   2007
  • Volume/Section/Page Volume 17: 669-681
  • Web Address   http://genome.cshlp.org/content/17/6/669
  • [3] Author   T.H. Morgan et al.
  • Title   The Mechanisms of Mendelian Heredity
  • Publication  Science
  • Date   1916
  • Volume/section/page Volume 44, Issue 1137, Pages 536-543
  • [4] Author   A.H. Sturtevant
  • Title The linear arrangement of sx sex-linked factors in Drosophila, as shown by their mode of association
  • Publication  Journal of experimental zoology
  • Date   January 1913
  • Volume/section/page Volume 14, Issue 1, Pages 43-59
  • [5] Author   Beadle, GW. and Tatum E.L.
  • Title   Genetic control of biochemical reactions in Neurospora
  • Publication  PNAS
  • Date   1941
  • Volume/section/page Volume 27, Pages 499-506
  • [6] Author   Muller H.J.
  • Title   Artificial transmutation of the gene
  • Publication  Science
  • Date   1927
  • Volume/section/page Volume 46, Pages 84-87
  • [7] Author   Griffith, F.
  • Title   The significance of pneumococcal types
  • Publication  J. Hyg. (London)
  • Date   1928
  • Volume/section/page Volume 27, Pages 113-159
  • [8] Author   Avery, O.T. et al.
  • Title Studies on the chemical nature of the substance inducing transformation of pneumococcal types
  • Publication  J. Exp. Med.
  • Date   1944
  • Volume/section/page Volume 79, PAges 137-158
  • Web addess   http://www.ncbi.nlm.nih.gov/pubmed/20474956?dopt=Abstract
  • [9] Author   Hershey, A.D., Chase, M.
  • Title                     An upper limit to the protein content of the germline substance of bacteriophage  T2
  • Publication  Virology
  • Date   1955
  • Volume/section/page Volume 1, Pages 108-127
  • [10] Author   Watson, J.D. and Crick, F.H.C
  • Title   Genetic implications of the structure of deoxyribonucleic acid
  • Publication  Nature
  • Date   1953
  • Volume/section/page Volume 171, Pages 964-967
  • Web addess   http://www.ncbi.nlm.nih.gov/pubmed/13063483?dopt=Abstract
  • [11] Author   Crick, F.H.C
  • Title   On protein synthesis
  • Publication  Symp. Soc. Exp. Biol.
  • Date   1958
  • Volume/section/page Volume XII, Pages 138-163
  • [12] Web addess  http://www.genomenewsnetwork.org/resources/timeline/1973_Boyer.php
  • [13] Web addess   http://www.genome.gov/10001772
  • [14] Author   Hester M. Wain et al.
  • Title   Guidelines for Human Gene Nomenclature
  • Publication  Genomics
  • Date   April 2002
  • Volume/section/page Volume 79, Issue 4, Pages 464-470
  • Web addess   http://www.sciencedirect.com/science/article/pii/S0888754302967480
  • [15] Author   Pearson H.
  • Title   Genetics: What is a gene?
  • Publication  Nature
  • Date   May 25, 2006
  • Volume/section/page 441 (7092): 398-401
  • Web addess  http://www.ncbi.nlm.nih.gov/pubmed/16724031?dopt=Abstract

 

FURTHER READING

  1. http://www.jbc.org/content/279/39/40247.full Robert Sinsheimer’s personal account of what he witnessed for the past 60 years as molecular biology exploded as a branch of biology.
  2. Reference 2 provides a nice overview of the “gene” concept and how genes are viewed in today’s biology. It also provides resources if you want to explore. http://genome.cshlp.org/content/17/6/669
  3. “A History of Molecular Biology” written by Michael Morange is one of the well wrtitten books which introduces molecular basis of life in a step-wise and clear manner. ISBN: 0674001699
  4. www.genome.gov Official website of the NIH’s, National Human Genome Research Institute provides a lot of interesting informations in lots areas.