Wednesday, May 04, 2016

HUMAN GENE EDITING: A summary overview of the science, research, regulations, ethics and hazards of Gene Editing/CRISPR

An International Summit on Human Gene Editing hosted by the US National Academy of Sciences, the US National Academy of Medicine, the UK Royal Society and the Chinese Academy of Sciences took place on December 1-3, 2015 in Washington to discuss the scientific, ethical, legal and regulatory issues associated with "Gene Editing" human DNA for both research, clinical and personal "enhancement" applications. A summary of the Summit is available at the following link.  Following the Summit, the Organizing Committee Members issued the following Summit Statement on Gene Editing human DNA for research and its potential applications.

"Committee of Experts" has also been selected and mandated to "perform its own independent and in-depth review of the science and policy of human gene editing by reviewing the literature and holding data-gathering meetings in the U.S. and abroad to solicit broad input from researchers, clinicians, policymakers, and the public. The committee will also monitor in real-time the latest scientific achievements of importance in this rapidly developing field. Finally, while informed by the statement issued by the organizing committee for the international summit, the study committee will have broad discretion to arrive at its own findings and conclusions, which will be released in a peer-reviewed consensus report. Expected to be completed in late 2016, the report will represent the official views of NAS and NAM." Source: 

The Committee held its first meeting in February 2015 in Washington to discuss the scientific, medical, legal, regulatory and ethical issues surrounding Gene Editing of human DNA. The Committee also organized both a workshop in Paris in April 2015 hosted by the Federation of European Academies of Medicine to "focus on the state of the science and international regulatory landscape regarding human gene editing," as well as a meeting at the French National Academy of Medicine in Paris "focused on the principles underlying human gene editing governance and policy." You can view both events at this link and you can watch a video of the Paris meeting at the following linkDetails about the Committee's work and study is available at this link

Science, Research, Regulations, Ethics and Hazards of Gene Editing/CRISPR 

Gene "editing" human DNA - the sacrosanct essence and blueprint of Life - poses a myriad of extremely alarming issues and irreversible hazards to the very essence, nature and future survival of humanity and of all Life on this planet. As the Committee members of the Summit themselves admit and write in the Summit Statement

"Gene editing might also be used, in principle, to make genetic alterations in gametes or embryos, which will be carried by all of the cells of a resulting child and will be passed on to subsequent generations as part of the human gene pool. Examples that have been proposed range from avoidance of severe inherited diseases to ‘enhancement’ of human capabilities. Such modifications of human genomes might include the introduction of naturally occurring variants or totally novel genetic changes thought to be beneficial. 

Germline editing poses many important issues, including: (i) the risks of inaccurate editing (such as off-target mutations) and incomplete editing of the cells of early-stage embryos (mosaicism); (ii) the difficulty of predicting harmful effects that genetic changes may have under the wide range of circumstances experienced by the human population, including interactions with other genetic variants and with the environment; (iii) the obligation to consider implications for both the individual and the future generations who will carry the genetic alterations; (iv) the fact that, once introduced into the human population, genetic alterations would be difficult to remove and would not remain within any single community or country; (v) the possibility that permanent genetic ‘enhancements’ to subsets of the population could exacerbate social inequities or be used coercively; and (vi) the moral and ethical considerations in purposefully altering human evolution using this technology." 

Earlier in 2015, several American scientists including two Nobel Prize winners called for a debate on the genetic engineering of humans, warning that the technology able to change the DNA of future generations is now “imminent.” Meanwhile, Another group of scientists published a statement in which they said that it was “irresponsible” to create genetically modified babies/humans at this point in time without ruling out the possibility and desire to do so in the future: " Almost everyone says it’s premature for clinical use and there should be a delay, but it doesn’t mean it should be ruled out forever; it’s like stem-cell research. It needs to be regulated but without too much constraint or endangering the whole enterprise.” said Richard Hynes, the MIT cancer biologist who co-chairs the Human Gene Editing study. A separate group of scientists working within the biotech industry have also published a statement warning that “scientists should agree not to modify the DNA of human reproductive cells” because it raises safety and ethical risks including the danger of “unpredictable effects on future generations.” 

Gene Editing precise, accurate and efficient ?

Dr. Jonathan Latham - a prominent scientific expert on biotechnology - debunks the myths surrounding the incessantly repeated misleading and fraudulent claims of the purported "precision," "accuracy" and "efficiency" of Gene Editing/CRISPR. 

Dr. Latham alarmingly writes that Gene Editing “can induce mutations at sites that differ by as many as five nucleotides from the intended target”, i.e. CRISPR may act at unknown sites in the genome where it is not wanted (u et al., 2014).  So far, it is technically not possible to make a single (and only a single) genetic change to a genome using CRISPR and be sure one has done so (Fichtner et al., 2014). As Fichtner noted “in mammalian systems Cas9 causes a high degree of off-target effects”. And at least until modified versions come into use, this will limit the safety, and hopefully limit the application, of CRISPR and related biotechnologies. There is, furthermore, no guarantee that more precise versions of CRISPR are even biologically possible. Technically therefore, precision is a myth: no form of genome editing can do what is currently being claimed. 

The second key error of CRISPR boosters is to assume that, even if we had complete precision, this would allow control over the consequences for the resulting organism. A classic example of how DNA can still reveal unexpected functions decades after discovery is the CaMV 35S promoter, a DNA sequence used in commercialised GMO plants for almost twenty years. The CaMV 35S DNA is described in every application for commercial use as a simple DNA “promoter” (an “on” switch for gene expression). 

In 1999, however, the CaMV 35S “promoter” was found to encode a recombinational hotspot (Kohli et al., 1999). In 2011 it was found to produce massive quantities of small RNAs. These RNAs probably function as decoys to neutralise the plant immune system (Blevins et al., 2011). One year later still, regulators found it to contain an overlapping viral gene whose functions are still being elucidated (Podevin and du Jardin 2012).  Will we ever know enough about any DNA sequence to accurately describe changing it as “editing”? 

The third error of CRISPR advocates is to imply that changes to gene functions can be presumed to be discrete and constrained. The concept of the precise editing of a genome leading to a precise biological outcome depends heavily on the conception that genes give rise to simple outputs. This is the genetic paradigm taught in schools. It is also the paradigm presented to the public and that even plays a large role in the thinking of molecular genetic researchers.

However, a defined, discrete or simple pathway from gene to trait probably never exists. Most gene function is mediated murkily through highly complex biochemical and other networks that depend on many conditional factors, such as the presence of other genes and their variants, on the environment, on the age of the organism, on chance, and so forth. Geneticists and molecular biologists, however, since the time of Gregor Mendel, have striven to find or create artificial experimental systems in which environmental or any other sources of variation are minimised so as not to distract from the more “important” business of genetic discovery. 

But by discarding organisms or traits that do not follow their expectations, geneticists and molecular biologists have built themselves a circular argument in favour of a naive deterministic account of gene function. Their paradigm habitually downplays the enormous complexities by which information passes (in both directions) between organisms and their genomes. It has created an immense and mostly unexamined bias in the default public understanding of genes and DNA. This is not my argument. It belongs to Richard Lewontin of Harvard University, probably the most famous geneticist of our time." Source: 

Several other prominent scientists and researchers have also debunked the myths regarding the oft-repeated misleading claims of precision and accuracy of Gene Editing/CRISPR.  
Gene Editing Research

Chinese scientists were the first researchers in the world to edit the genomes of "non viable" human embryos.  The Chinese researchers unsuccessfully attempted to modify the gene responsible for β-thalassaemia, a potentially fatal blood disorder, using a gene-editing technique known as CRISPR/Cas9. However, in a published paper, the researchers explain and admit that their experiments were a total failure and they reveal serious obstacles to using Gene Editing/CRISPR in medical applications. 

"The scientist injected 86 embryos and then waited 48 hours, enough time for the CRISPR/Cas9 system and the molecules that replace the missing DNA to act — and for the embryos to grow to about eight cells each. Of the 71 embryos that survived, 54 were genetically tested. This revealed that just 28 were successfully spliced, and that only a fraction of those contained the replacement genetic material. “If you want to do it in normal embryos, you need to be close to 100%,” Huang says. “That’s why we stopped. We still think it’s too immature.”
The researchers also found a surprising number of ‘off-target’ mutations assumed to be introduced by the CRISPR/Cas9 complex acting on other parts of the genome. This effect is one of the main safety concerns surrounding Germline gene editing because these unintended mutations could be harmful. The rates of such mutations were much higher than those observed in gene-editing studies of mouse embryos or human adult cells. And Huang notes that his team likely only detected a subset of the unintended mutations because their study looked only at a portion of the genome, known as the exome. “If we did the whole genome sequence, we would get many more,” Huang alarmingly admits. 

"I believe this is the first report of CRISPR/Cas9 applied to human pre-implantation embryos and as such the study is a landmark, as well as a cautionary tale," says George Daley, a stem-cell biologist at Harvard Medical School in Boston, Massachusetts. "Their study should be a stern warning to any practitioner who thinks the technology is ready for testing to eradicate disease genes." Source:
Other scientists have also warned about the dangers of Gene Editing DNA in human embryos:
"In our view, genome editing in human embryos using current technologies could have unpredictable effects on future generations. This makes it dangerous and ethically unacceptable. Such research could be exploited for non-therapeutic modifications." 
However, despite the alarming findings and dismal failure of the first Chinese experiment editing "non-viable" human embryos and the warnings of other researchers about the hazards of Gene/Germline Editing/CRISPR, another team of researchers in China have alarmingly recently reported "editing" the genes of "non viable" human embryos to try to make them resistant to HIV infection. Their published paper is the second published claim of gene editing human embryos using CRISPR. 

In February 2016, research scientists in London/UK have alarmingly been granted permission by the UK Human Fertilisation and Embryology Authority (HFEA) to "edit" the genomes of "viable" human embryos for research. The approval by the UK HFEA represents the world's first regulatory approval of Gene Editing using CRISPR on "viable" human embryos for research. 

On April 22, 2016 a Japanese government bioethics panel approved gene modifications of fertilized human eggs for research purposes.
Regulatory Framework
The EU law regulating GMO's defines a GMO as: "Any organism, with the exception of humans, in which the genetic material (DNA) has been altered in a way that does not occur naturally by mating or natural recombination”Source:
According to a recent expert legal opinion published by EU legal experts Tade Spranger and Ludwig Krämer, animals, plants and other living organisms whose genes have been "edited" using Gene Editing/CRISPR fall under the EU definition of GMO's and should therefore be regulated under the EU law regulating GMO's. 

However, both the industry and the US administration are lobbying regulatory agencies in both the EU i.e. European Commission and in the US to deregulate Gene Editing/CRISPR by fraudulently arguing that living organisms i.e. animals, plants, etc. whose genes have been "edited" do not contain foreign DNA and therefore should not be regulated as a GMO. The following document provides an overview of US pressure to deregulate Gene Editing in the EU. 
In the US, the USDA has approved and deregulated a gene-edited corn from Dupont and deregulated and approved a Gene Edited mushroom: “APHIS does not consider CRISPR/Cas9-edited white button mushrooms as described in your October 30, 2015 letter to be regulated,” the agency wrote in a April 13 letter to the applicant. 
However, the federal US National Institute of Health (NHI) has stated that it will not provide funding for Germline editing; in a published letter, the NHI stated: NIH will not fund any use of gene-editing technologies in human embryos. The concept of altering the human germline in embryos for clinical purposes has been debated over many years from many different perspectives, and has been viewed almost universally as a line that should not be crossed. Advances in technology have given us an elegant new way of carrying out genome editing, but the strong arguments against engaging in this activity remain. These include the serious and unquantifiable safety issues, ethical issues presented by altering the germline in a way that affects the next generation without their consent, and a current lack of compelling medical applications justifying the use of CRISPR/Cas9 in embryos."   

Not only is the science primitive, deeply flawed and extremely hazardous, but it is also highly unethical. In fact, DNA is the sacrosanct essence and blueprint of human life and of all Life on this planet. Therefore, it is both highly unethical and extremely hazardous to allow mad and morally bankrupt pseudo-scientists suffering from severe megalomania to play God and Lego with our DNA and by extension with the DNA of countless yet unborn future generations. 


Moreover, Gene/Germline Editing/CRISPR can and will be misused for eugenics purposes. 
Eugenics was embraced and infamously practiced by Hitler and the NAZI's during WW2 to sterilize and kill hundreds of millions of so-called “inferior” members of the human race i.e. Jews, the crippled, the feeble-minded, etc. under the NAZI's racial purification theory and program (i.e. Holocaust) and the purported and proclaimed superiority of the so-called “Aryan” master race. 

However, eugenism as an offshoot of the Darwinian theory of evolution and racial superiority (i.e. Survival of the fittest) took roots both in the UK and in the US well before the rise to power of Hitler; in fact eugenics was embraced, preached, financed and practiced by a large majority of the Darwinian ruling and moneyed so-called "elite" in the US in the early twentieth century. 

Unfortunately eugenism has not died with Hitler; in fact, it has been resurrected and is covertly practiced throughout the world through scientific and technologically more advanced tools and means i.e. through the forceful and mandatory administration of sterilizing/poisonous vaccines, fluoridated water, toxic GMO's, poisonous chemicals copiously sprayed on our food crops, soil, water, air and environment, by many of the same ruling and moneyed families and corporations that embraced, preached, financed and practiced eugenism both in the US and in Nazi Germany. 

The methods have changed but the actors and the objectives remain unchanged. In fact, many of the same ruling and moneyed so-called "elite" families that embraced eugenism in the US in the early 20th century are today major funders and shareholders of the biotech/chemical/pharmaceutical industry. And many of the biotech/chemical/pharmaceutical corporations that today manufacturer toxic vaccines, genetically modify our food crops and copiously spray their poisonous chemicals on our food supply, soil, water, air and environment are remnants and offshoots of the infamous IG Farben – the Nazi petrochemical industrial conglomerate. Toxic food for thought...

Suffice it here to predict and to warn that Gene/Germline Editing/CRISPR will also – like GMO's - be patented, exploited and misused by profit-oriented corporations, corrupt and criminal fascist governments, the Military Industrial Complex and the Darwinian ruling and moneyed “elite” for profit, power, control, eugenics, war and other malevolent purposes and destructive ends. 

Several books  could be written on the links between biotechnology and eugenics. It is infantile, primitive and beyond stupid for the proponents and advocates of eugenics to claim and to believe that they can produce a race of “supermen” using Gene/Germline Editing/CRISPR. You cannot simply delete “stupid” genes and replace them with “intelligent” ones; or “cut” so-called “undesirable” or “faulty” genes and “copy” and “paste” desirable ones for good health, intelligence, wisdom, integrity, etc. Instead of creating a class of so-called “supermen,” the mad scientists and their sponsors will create monstrous human chimeras and irreversibly alter and destroy human DNA in the process...

Legal issues:

There are also crucial legal issues that need to be addressed and answered; for instance, corporations and governments can and will patent, exploit and misuse the Gene/Germline Editing/CRISPR technology. What would be the resulting legal consequences on the lives of humans and their offsprings who had their genes “edited” ? What would be the legal definition and the legal rights of a genetically modified embryo and human being...? And who would own the resulting genetically modified embryo and human being...? 


To summarize and to conclude, the science is not only primitive, flawed, extremely dangerous and unregulated but also highly unethical. Gene/Germline Editing/CRISPR will literally and irreversibly change our DNA and the DNA of all yet unborn future generations - the sacrosanct essence and blueprint of human Life and of all Life on this planet.

We cannot allow mad and morally bankrupt scientists suffering from severe megalomania play God and Lego with our DNA. Corporations, governments and the Industrial Military Complex can and will patent the technology and can and will exploit and misuse the technology for profit, power, control, eugenics, war and other malevolent and destructive ends. Human history is filled with repeated, countless and endless tragic examples of science and technology being misused for profit, power, control, war and other malevolent and destructive ends.

If humanity allows mad and morally bankrupt pseudo-scientists and their sponsors to play God and “edit” their DNA, humanity will open Pandora's box and wake up in a monstrous dystopian world of genetically modified human chimeras and other monstrous chimeras life forms in next 15-30 years...

Gene Editing/CRISPR classified as a Weapon of Mass Destruction

Gene/Germline Editing/CRISPR poses a greater threat and danger to the very near future survival of humanity and of all Life on this planet than nuclear weapons and all the Weapons of Mass Destruction devised by “scientists” and used against humanity to this day. In fact, James Clapper, U.S. director of national intelligence, has recently alarmingly added and classified Gene Editing/CRISPR to a list of threats posed by “weapons of mass destruction and proliferation” in his Worldwide Threat Assessment of the US Intelligence Community. 

“Given the broad distribution, low cost, and accelerated pace of development of this dual-use technology, its deliberate or unintentional misuse might lead to far-reaching economic and national security implications. Research in genome editing conducted by countries with different regulatory or ethical standards than those of Western countries probably increases the risk of the creation of potentially harmful biological agents or products,” the report alarmingly states.

"The intelligence assessment drew specific attention to the possibility of using CRISPR to edit the DNA of human embryos to produce genetic changes in the next generation of people—for example, to remove disease risks. It noted that fast advances in genome editing in 2015 compelled “groups of high-profile U.S. and European biologists to question unregulated editing of the human germ line (cells that are relevant for reproduction), which might create inheritable genetic changes.

So far, the debate over changing the next generation’s genes has been mostly an ethical question, and the report didn’t say how such a development would be considered a WMD, although it’s possible to imagine a virus designed to kill or injure people by altering their genomes," writes Antonio Regalado, senior editor for biomedicine at MIT Technology Review. 

Hopefully humanity will wake up from its deadly slumber before it wakes up in a dystopian world of monstrous genetically modified human chimeras... 

Note: I will be updating this post as the issue evolves..

Update (13/05/16)

- Scientists hold private meeting at Harvard to discuss "creating synthetic humans genomes from scratch, by stringing together off-the-shelf DNA letters..."  

- Scientists create first "gene edited" hornless dairy cow.

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