Beyond Human: Engineering Our Future Evolution

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While this technology continues to touch every industry from aerospace to automotive parts, its most life-changing application lies in the medical arena. By building biological structures layer by layer, bioprinters can craft anything from bladders to bone, and skulls to skin. The above is an excerpt from the screenplay of The Fifth Element , a Luc Besson sci-fi epic set in the twenty-third century. The movie begins with a Mondoshawan spacecraft on its way to Earth to bring back the Fifth Element but the spaceship is destroyed by the evil Mangalores.

Fortunately, some genetic material of the Fifth Element is salvaged and a team of scientists use the DNA remains to rebuild bioprint the Supreme Being, Leeloo, which is what is happening in the above excerpt. Humans are fragile organisms. Today, it is nuts and bolts engineering that allows us to explore the ocean depths and journey into space, but in the future it might be a different kind of engineering that allows us to survive—and even thrive—in extreme environments. Here are some examples. It is June Your job as an astronaut was determined before you were born as part of a pre-birth contract that paid for your genetic design.

Your father had always wanted to be an astronaut but never made it to the final round of interviews and instead made a career as a military pilot. Your father, being the vain type, decided to clone himself, so you have his blue eyes, his brown hair, and even a birthmark on your right shoulder. Unlike your father, you have never been ill because you were screened for genetic diseases and were gifted a customized genetic heritage based on professional astronauts, so you have just the right temperament, intelligence, and leadership to do the job.

For this closing chapter we revisit Blade Runner. As a sci-fi fan and popular science writer, I usually assess the importance of a sci-fi film by its ability not only to engage in prediction and foresight, but also to portray plausible futures. This is why Blade Runner could also be categorized as a future-realism movie. Today, given the potential for human engineering and cloning, Blade Runner has never been more relevant.

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Title Beyond Human. Whole-chromosome painting probes, chromosome-arm painting probes, and centromeric, subtelomeric, and locus-specific probes are some of the examples which are available for the detection of specific constitutional and acquired chromosomal abnormalities. Hybridizing all 24 different human chromosomes with whole-chromosome painting probes labeled with a combination of 5 different fluorophores enables visualizing each chromosome with a specific color.

FISH also enabled showing that chromosomes are compartmentalized into discrete territories in the nucleus [ 26 ]. A correlation between the location and the size and the gene content of the chromosomes was described. Smaller and gene-rich chromosomes are generally situated towards the interior whereas larger and gene-poor chromosomes are generally situated towards the periphery of the nucleus [ 27 , 28 ]. In light of these studies, several clinical diagnostic FISH tests have become commercially available.

The most remarkable one is the test for deletion or duplication of the subtelomeric regions leading to a clinical picture mostly characterized by multiple congenital anomalies and intellectual disability. Being time-consuming and expensive to evaluate chromosomal rearrangements in the whole genome by FISH led to the development of new techniques such as array-based comparative genomic hybridization [ 33 — 35 ].

Comparative genomic hybridization CGH which is based on competitive hybridization of amplified tumor DNA and normal DNA hybridized on normal metaphase slide was first developed by Kallioniemi et al. If we look at the evolution of genetic technologies, the emergence of new technologies has always been inevitable due to the necessities revealed by the previous technologies. Although hybridization-based methods, which allow screening RNA, DNA, or protein such as northern blot, southern blot, or western blot, respectively, are widely used, innovative and powerful microarray hybridization methods were developed in the s.

Instead of hybridizing a labeled probe to targeted DNA on a slide, with array-CGH, the patient's DNA is hybridized to a large number of well-characterized probes immobilized on a slide. To summarize briefly, in this method, DNA of the patient is labeled with a specific color green and mixed with exactly the same amount of DNA of a normal control, which is labeled with a different color red. This DNA mixture is then hybridized to the denaturated probe DNA on the glass and signal intensity ratios of test over reference are measured.

Yellow dye appears when both patient and reference DNA are equal in proportion because of the presence of the same amount of red and green dyes, while regions with copy number losses are visualized as red and gains are green. This technique permits the detection of whole genome copy number variation CNV duplications and deletions at high resolution [ 36 ]. Array-CGH failed to detect the recessive disease genes, mosaic aneuploidy, uniparental disomy UPD , or heterochromatic rearrangements.

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These arrays have the highest resolution of all of the available array-based platforms. Combination of array-CGH and SNP genotyping in a single platform increases the clinical diagnostic capability and uncovers the detection of small copy number variants [ 39 ]. The major drawback of array-based CGH is that it can only detect unbalanced rearrangements and is unable to detect balanced aberrations such as chromosome translocations, inversions, and insertions. However, recently, a modified array protocol, called translocation CGH tCGH , was developed to address recurrent translocation breakpoints [ 40 ].

Larger genomic changes such as deletions, duplications, and translocations can be detected by conventional karyotyping, FISH, or array-CGH methods but single nucleotide changes cannot be detected by these techniques. Molecular genetic techniques were rapidly developed after the establishment of polymerase chain reactions that enabled generating thousands to millions of copies of a particular DNA sequence [ 41 ].

Although PCR was developed only a few decades ago, it has found numerous basic and clinical applications and is indispensable in today's science. Automation of PCR was greatly facilitated and simplified the detection of genomic mutations. SSCP and RFLP, the most widely used techniques for mutation screening method in genetic diagnostic laboratories, were not able to detect every mutation, so development of new methods was needed.

If the sequence of the gene of interest is not known, it may be difficult to interpret the results of these techniques. The determination of DNA sequencing enabled identifying the definite nucleotide changes in the targeted genes. This necessity was overcome by Maxam and Gilbert introducing Maxam-Gilbert chemical sequencing technology based on chemical modification of DNA followed by cleavage at specific bases [ 43 ]. Despite the efficiency of Maxam-Gilbert sequencing method, the use of hazardous chemical and inability to read long PCR fragments made this method replaced by Sanger sequencing that was based on dideoxynucleotide chain termination [ 44 ].

Manual Sanger sequencing method has been improved by the introduction of first generation of automated DNA sequencers [ 45 ]. Automatization of DNA sequencing enabled sequencing human genome in a fast and accurate way. With the advances in the field of molecular genetics, it became possible to launch the Human Genome Project to reveal the complete human genome. The programme was launched in the USA with an effort of the Department of Energy and the National Institutes of Health in collaboration involving 20 groups in One day later, in parallel with HGP, Craig Venter who launched a human genome sequencing project by Celera Genomics using shot-gun sequencing method published the whole human genome sequence in Science [ 47 ].

The project was declared to be finished two and a half years ahead of scheduled time in coinciding with the 50th anniversary of the paper in which Watson and Crick reported DNA's double helix [ 48 ].


Human Genome Project not only revealed the complete sequence of the human genome but also led to a huge improvement in the sequencing technology. Amplification of the gene of interest in the affected individual s enabled revealing mutations associated with specific monogenic disorders.

Although automation of traditional dideoxy DNA sequencing Sanger method increases the efficiency of DNA sequencing, it was still not cost- and time-effective. A new technology called massively parallel sequencing MPS erasing these disadvantages was developed by Lynx Therapeutics [ 49 ]. This technology using reads of multiple reactions simultaneously and generating large amounts of sequence data in parallel provided a large impetus for exome sequencing, whole genome sequencing, and transcriptome and methylation profiling.

NGS technology is widely used for a variety of clinical and research applications, such as detection of rare genomic variants by whole genome resequencing or targeted sequencing, transcriptome profiling of cells, tissues, and organisms, and identification of epigenetic markers for disease diagnosis. One of the most successful applications of NGS technology is genome-wide discovery of causal variants in single gene disorders and complex genomic landscapes of many diseases.

While whole genome or whole exome sequencing is the most comprehensive strategy in the diagnosis of unknown diseases and identification of new disease genes, targeted sequencing using selected panels of genes can reduce the sequencing time and cost by combining the diseases in the same group or pathway genes in known clinical pictures such as intellectual disability, neurometabolic disorders, or malignancies [ 50 ]. In addition to cost-effective advantages, sequencing the small part of the genome allows reducing the number of variations that in turn reduce the cost and time needed for data interpretation [ 51 ].

Targeted sequencing opened a new window in the diagnosis of several diseases with unknown etiology. Following the rapid advances in NGS technologies, the role of NGS in routine clinical practice will increase exponentially. Noninvasive prenatal diagnosis by using NGS is another application of this new technology. The most important step in the prenatal diagnostic procedures is obtaining fetal material to evaluate genetic condition.

For years, invasive and noninvasive tests have been used to assess the fetal health, particularly chromosomal abnormalities, during the pregnancy.

Noninvasive tests measure epiphenomena, which does not analyze the pathology underlying the clinical picture of interest. Their sensitivity and specificity have not also reached the expected level despite several studies. On the other hand, invasive tests have been found to be associated with significant risks for both the mother and fetus. The identification of cell-free fetal DNA in maternal circulation and analyzing this fetal material by using NGS opened up a new horizon in the field of reproductive medical care.

Despite main advantages of NGS technology, the researchers and clinicians still have many concerns about the implementation of NGS in practice [ 52 ]. The interpretation of huge amount of data obtained by NGS technology, billing and insurance issues, duration and content of consent process, and disclosure of incidental findings and variants of unknown significance were the main challenges related to offering this technology [ 53 ].

Approximately 10 years ago, karyotyping was the gold standard in patients with intellectual disability but array-CGH analysis has become the first line diagnostic test replacing karyotyping and FISH nowadays. As evident from this example, approaches to the genetic-related diseases could change in parallel with the advances in technology and science. In , a small chromosome called Philadelphia chromosome was identified to be the cause of the chronic myeloid leukaemia CML.

Evolution of Genetic Techniques: Past, Present, and Beyond

It was shown in by the chromosome banding technique that this chromosome was a result of a translocation between chromosomes 9 and 22 [ 54 , 55 ]. The following studies revealed that this fusion gene resulted in activation of a tyrosine kinase, which led to the discovery of a tyrosine kinase inhibitor drug Gleevec that was shown to be a highly successful treatment for CML [ 57 ].

Genetic test that will be used in the diagnosis should be chosen very carefully, which might not be the newest or the most sophisticated one. Sometimes only a karyotype could be enough to identify the genetic condition in the patient instead of more complicated array-CGH or NGS methods. As the technology in genetics rapidly evolves, new insights in terms of data interpretation and genetic counseling including pretest counseling, return of results, and posttest counseling need to be considered. Databases and consortium reports regarding the experiences of the clinicians and geneticists are crucial for integration of genomics into clinical practice.

If the developments in genetics and computer technologies continue to progress at their current speed, history has shown us we can look forward to some amazing developments in human life in the very near future. Some realistic scenarios of human life in the future could even see us carrying identity cards, which include our genome characteristics, rather than the format we are currently using.

Gene corrections, cloned individuals and organs, and even genetic-based techniques as a primary laboratory analysis in almost all human diseases for a clinician will no longer be a dream. We have come to the point nowadays where genetic testing is commercially available; the individual now has the possible means to access this delicate information named as direct to consumer DTC genetic testing. Contrary to the traditional hospital or physician based testing, accessing an individual's genetic information without medical or specialized interpretation has gradually been finding a place in our daily lives.

Today, more than 25 companies, from all over the world, offer DTC service to the public.

Engineering Our Future Evolution

Serious concerns, however, regarding the use of this kind of service, have been raised in terms of misleading and incidental results derived from unproven or invalidated data. Moreover, there is also a significant risk for unauthorized use of sensitive genetic information by big business, particularly in the fields such as health insurance. On the other hand, DTC does provide early awareness of genetic diseases and thereby offers individuals the opportunity to play an active role in their own health care.

The issue at stake here leads us to the same difficult medical ethics dilemma: patient autonomy and right to know one's genetic composition versus nonmaleficence. To conclude, in parallel with the rapid developments in the field of genetic technologies, ethical and legal issues regarding the implementation of those technologies need to be addressed. Because use of personal genetic information looks certain to directly impact our daily lives in the near future, protocols need to be discussed in detail, with guidelines provided and updated regularly as part of a regulated multidisciplinary approach.

The authors declare that there is no conflict of interests regarding the publication of this paper. National Center for Biotechnology Information , U. Journal List Biomed Res Int v. Biomed Res Int. Published online Mar Author information Article notes Copyright and License information Disclaimer. Received Aug 12; Accepted Dec 5. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

This article has been cited by other articles in PMC.

Evolution of Genetic Techniques: Past, Present, and Beyond

Abstract Genetics is the study of heredity, which means the study of genes and factors related to all aspects of genes. Introduction Due to rapid advances in genomic technologies, genetics analyses have become essential in clinical practice and research. This Humble Book Bundle lets you grab sci-fi books by space psychologists, astrophysicists, geneticists and other scientists, while raising money for charity. Science fiction can be extra enjoyable when it's written by real scientists. The latest Humble Book Bundle offers sci-fi novels written by practicing scientists specializing in genetics, astrophysics and psychology.

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