Messing with sacred laws

GENETICS

The impact of gene editing on our own species offers both the greatest promise and, arguably, the gravest risk for the future of humanity

By GELINDE NAREKINE
WE humans have been reshaping the physical world since the day we started roaming on the surface of the Earth.
But the effects have never been as dramatic as they are today.
Many exercises we pursued in the name of survival and civilisation have a negative downside that now remain to haunt us.
On a broader scale, our quest for sophistication also has negative impacts on our environment and our livelihood.
For instance, industrialisation, which has contributed massively to increasing our standard of living, continues to cause climate changes and other mishaps that threaten ecosystems around the globe.
The world’s freshwater and aquatic systems have been pushed into extreme stress levels.
And, along with other human activities, a surge in species extinction has been precipitated, that is destroying the diverse populations of plants and animals, with whom we share this planet.
The biological world is also undergoing massive human-induced changes.
Scientists believe, by Charles Darwin’s theory of evolution, it took organisms billions of years to develop through a series of random genetic variations.
Some of which conferred advantages in survival, competition, and reproduction.
However, with the emergence of agriculture some 10,000 years ago, humans began manipulating the process of evolution through selective breeding of plants and animals in order to produce desired outcomes.
Today, scientists have succeeded in bringing this biological process fully under control.
Using powerful tools of biotechnology to tinker with DNA – deoxyribonucleic acid, the hereditary material inside all living cells, where information is stored as a code of chemical bases organised in a series of different combinations – scientists can now manipulate and rationally modify the genetic code that defines every species on Earth, including our own.
And with the newest and arguably, the most effective genetic engineering tool known as CRISPR, which stands for clustered regularly interspaced short palindromic repeats – an organism’s entire set of DNA content, has become almost as editable as a simple piece of text.
As long as the genetic code for a particular trait is known, scientists can use CRISPR to insert, edit, or delete the associated gene in virtually any living plant’s or animal’s genome – the entire set of DNA instructions found in a cell.
This process is far simpler and more effective than any other gene-manipulation technology in existence to date.
As such, we now find ourselves on the verge of a new age in genetic engineering and biological mastery, thus, a revolutionary era in which the possibilities are incomprehensible and somewhat, unpredictable.
What used to be simply creative imagination in science fiction, has become a practical reality, just overnight.
Animals have been the first and, so far, the biggest proving ground for this new gene-editing tool.
For instance, scientists have harnessed CRISPR to generate a genetically enhanced version of the beagle, a small hound dog breed popular as both pet and hunter – creating dogs with Schwarzenegger-like super-muscular physiques by making DNA changes to a gene that controls muscle formation.
In another case, by inactivating a gene in the pig genome that responds to growth hormone, researchers have created micro-pigs, which are no bigger than large cats.
And, as we speak, genomes of more and more animals have been subjected to such experiments to see the physical variations in real life.
This technology has been widely deployed to fine-tune and upgrade crop genomes as well, paving way for agricultural advances that could dramatically improve people’s diets and ship up the world’s food security.
Experiments have produced disease-resistant rice, tomatoes that ripen more slowly, soybeans with healthier polyunsaturated fat content, potatoes with lower levels of a potent neurotoxin, and the list goes on.
Some of the benefits to human health are likely to come from using CRISPR on animals and even insects.
Few years back, experiments were carried to “humanise” the DNA of pigs.
The idea is to raise pigs that would someday serve as compatible organ donors for humans.
The genomes of new mosquito strains have also been manipulated, as to rapidly drive new traits into wild mosquito populations.
With this approach, scientists hope to eventually eradicate mosquito-borne illnesses such as malaria and Zika, or perhaps, even wipe out the disease-carrying mosquitoes themselves.

First attempt at editing human DNA
While applications on Earth’s flora and fauna are exciting, the human species too is being shaped by this process.
The impact of gene editing on our own species offers both the greatest promise and, arguably, the gravest risk for the future of humanity.
In mid-2015, while the world was still debating and deliberating on CRISPR research, Chinese scientists went ahead and published the results of their experiment on injecting CRISPR into human embryos. Despite the fact that they used discarded, nonviable embryos, their study was a major milestone in genetic engineering. That was the first-ever attempt to precisely edit the DNA of the human germline – the stream of genetic information connecting one generation to the next.
There is justifiable alarm over such developments. Yet, we cannot overlook the fantastic opportunities that gene editing presents in assisting people who suffer from unbearable genetic diseases. To treat many such diseases, CRISPR offers the potential to repair mutated genes directly in human patients.
For instance, this gene-editing tool has been used to correct the mutations responsible for cystic fibrosis – an inherited condition that causes severe damage to lungs and other organs – sickle cell disease – a genetic disorder in which the blood is damaged and cannot carry oxygen to the tissues – some forms of blindness, and severe combined immunodeficiency, among many other disorders.
Furthermore, researchers have corrected errors in DNA that cause Duchenne muscular dystrophy – a genetic disorder that causes muscle wasting and disability – by snipping out only the damaged region of the mutated gene, leaving the rest intact.
In the case of hemophilia A – a genetically inherited bleeding disorder in which the blood does not clot properly leading to spontaneous bleeding – researchers have harnessed CRISPR to precisely rearrange the disarray in DNA sequence implicated in this condition.
In addition, experiments have also been done to treat HIV/Aids.
Either by cutting the virus’s DNA out of a patient’s infected cells or by editing the patient’s DNA, the cells become resistant to infection altogether.
In 2018, again, Chinese scientists created history in editing the genome of twin girls by altering the gene of human cell surface component that the human immunodeficiency virus uses as receptor to infect the host.
It has been postulated that by doing so, scientists can now recreate humans to be resistant to HIV infection.
Assuming gene editing in humans proves to be safe and effective, it might seem logical, even preferable, to correct disease-causing mutations at the earliest possible stage of life.
Because CRISPR allows precise and relatively straight forward DNA editing, there is potential to transform every genetic disease into a potentially treatable target – at least, for every disease whose underlying mutation is known.
Yet, once it becomes feasible to transform an embryo’s mutated genes into “normal” ones, there will be temptation to upgrade normal genes to supposedly superior versions.
Should we begin editing genes in unborn children to lower their lifetime risk of diseases?
The quest for perfection seems almost intrinsic to human nature.
So, what about endowing unborn children with beneficial traits like greater strength and increased cognitive abilities, or changing physical traits, like eye, hair colour, or so on?
Given our brilliantly insane curiosity to tamper with things we know we don’t know, this course of direction looks somewhat, most likely.
Knowing the secrets of the entire human genome, researchers can more easily add, remove, or change regions of an organism’s DNA.
Working more like a pair of scissors – a molecular scissors – CRISPR cuts DNA at specific locations and either deletes sections or replaces them with alternative sequences.
Even so, it has the potential to performing even more complex and bizarre modifications of the human genome in real life and in real-time.
For the first time ever, we humans now possess this potent ability to edit not only the DNA of every living human, but also the DNA of future generations – in essence, to direct the evolution of our own species to the benefit of our curiosity and doubt.
The technology is so simple and yet so efficient that scientists could exploit it to modify the human germline.
In as much, this technology will someday, somewhere, be used to change the genome of our own species in ways that are heritable, forever, altering the genetic composition of humankind.
This is certainly, unprecedented in the history of life on earth, now and into the future.

Tricky moral issue
We are now forced to grapple with the tricky issue of where to draw the line when manipulating human genetics.
For this revolutionary scientific discovery has fanned not only the fires of hope and curiosity, but also of controversy, for both scientists and public alike.
Some people view such technology as wicked, a perverse violation of the sacred laws of nature and the dignity of life.
Others see the genome simply as software – something we can fix, clean, update, and upgrade, and argue that leaving human beings at the mercy of faulty genetics is not only irrational, but immoral.
In spite of every conceivable argument for or against, the danger and the risk of tinkering with the sacred laws of nature look so real.
And if our steps forward are not taken with caution, CRISPR technology could end up creating more bad than good for humanity as a whole.
Now more than ever, the incomprehensible reality of a man-made evolution gone wrong could be staring boldly at us.

Source of information: “A crack in creation: gene editing and the unthinkable power to control evolution,” by Doudna, JA and Sternberg, SH 2017.

• Gelinde Narekine works with the Discipline of Medical Laboratory Sciences, Division of Health Sciences, UPNG School of Medicine and Health Sciences.