Gene Editing, CRISPR and BioHacking- The Ultimate Frontier to Alter Humanity?
‘I have a mixed feeling about CRISPR, to be honest. On one hand, it feels awesome to be a part of it but on the other, it also brings a powerful sense of responsibility’- Dr. Jennifer Doudna, CRISPR Founder
This article is partly inspired by a Netflix documentary called Unnatural Selection which came out in Oct 2019. The limited series explains the groundbreaking advancement in gene editing technologies through CRISPR and the implication of BioHacking. It also deliberates on the moral and technological challenges which scientists and humans confront with this ground-breaking technology.
The series made me ponder over gene editing, DNA-editing technology of CRISPR (what’s the latest on this?!), and the new crop of biohackers who are running these experiments at home. As I dived deeper into these topics and their fascinating implications, I thought that this could be an interesting read for people keen to dive deeper into this area.
This piece intends to be an informative guide on these topics and is neither in support nor against these new technologies. Through the piece, I aim to uncover what is gene-editing/ bio-hacking, what happened to CRISPR, delve into its fascinating potential and concerns, and end with my views on what the future holds in this space.
Let’s begin!
What is Bio-Hacking?
What if you could cure genetic diseases like cancer, rare inherited ones like spinal muscular atrophy, and acquired vision loss for which scientists, doctors, pharma companies, and corporations have been trying to find a treatment for ages?
What if you could selectively edit genes to create stronger, healthier, physically more attractive babies, and what if you could edit your own genes to increase your life span by 20–30%,
More importantly what if you could rewrite the code of life in any organism and wrest control of evolution from nature itself?
Sounds fascinating and terrifying! That is what biohacking’s end game is all about.
Biohackers are people who experiment on their own bodies outside the purview of traditional medicine with the hope to boost physical or cognitive performance. This can include tracking your diet and sleep or pumping a younger person’s blood into your own veins in the hope to fight aging and other diseases associated with old age. (yes, people are doing this!).
Biohacking in its simplest form is not a new concept. Techniques like meditation, fasting, Vipassana have existed for long and can be counted in biohacking. Even selective breeding or artificial selection is being done for thousands of years on crops (GMO) and domestic animals.
Of late, some radical practices such as infrared saunas (escape stress from electromagnetic transmissions), virtual float tanks (induce meditative state through sensory deprivation), neurofeedback (training oneself to regulate brain waves) and cryotherapy (purposely making oneself cold) are also in use.
Biohacking in recent times has pushed the boundaries further by making your own body a playground for experimentation. The belief is that the general public should be made aware (agreed) and participate in scientific experimentations themselves (not so sure!) than leave this technology to test out in segregated labs.
It forms a branch of transhumanism, which holds that human beings should use technology to augment and evolve the species. This same theory is also the bedrock on which Elon Musk’s Neuralink has been formed to counter the growing threat of AI/ML as they become more advanced and intelligent.
On the regulation side, biohacking exists in a legal gray zone but is not outright illegal. The extent to which it should be regulated is as expected hotly contested. Some also feel that there is a class, income, elite revolution biohackers are up against as Josiah (star biohacker) mentions in his blog where he made a COVID 19 vaccine in his kitchen that worked!
Coming to the series, in one of the episodes, Tristan Roberts an HIV patient used gene therapy (N6 HIV) to lower the number of HIV particles in his blood in Oct 2017 and live-streamed it on FB. The treatment did not work unfortunately as his viral load went up.
Other examples shown from the biohacker community include a dog breeder who wants to eliminate genetic diseases in dogs and Josiah Zayner who provides gene editing kits by mail and is the first person who attempted to edit his own genes at a biotech conference!
But why has interest in biohacking picked up so much? What allows individuals with no medical or scientific background to tinker with this technology right at their homes?
For this, we need to go back to 2012 when CRISPR-Cas9 was discovered.
What is Clustered Regularly Interspaced Short Palindromic Repeats aka CRISPR?
Crispr was co-discovered by Dr. Jennifer Doudna in 2012 and is regarded as the biggest breakthrough in genetic science in this century. It’s a molecular toolkit that allows scientists to make precise changes in the genetic code of living organisms.
It comprises two components, a protein called Cas9 and a guide RNA. Together they create a tool that can be used to alter an organism’s genome with the system based on copying itself.
For instance, we can use CRISPR to edit and turn off one of the genes responsible for causing diabetes and increase insulin production.
Before CRISPR, researchers used to modify genes in cells that used to be time-consuming, difficult, and sometimes impossible. With CRISPR ‘Cas9’, the genetic scissors allow researchers to change the DNA of animals, plants, and micro-organisms with extremely high precision in the course of a few weeks!
The technique can help scientists develop drought-resistant crops, cure genetic disorders, eradicate infectious diseases, and develop better drugs, and research for all of this is ongoing.
In Oct20, Jennifer Doudna and Emmanuelle Charpentier were jointly awarded the Nobel prize in Chemistry for their work (becoming the 6th and 7th women to win the Nobel Prize in Chemistry!).
The technology and the ability to use RNA as a messenger have also been the foundation of Moderna and Pfizer vaccines for COVID!
The implications of CRISPR are immense and extend beyond the current pandemic. With the continuous evolution of genetic engineering, the timeline on the evolution of new species and treatment of diseases can dramatically collapse.
At present, the gene therapy treatment (to save lives) is expensive with some emerging drugs costing upwards of $500K.
But just as the opportunities are tantalizing so are the possibilities to take it beyond what has ever been experimented before.
And that is precisely what happened with the possibility to create designer babies which opened up a pandora’s box of moral and ethical implications that snowballed in 2018!
Why? Because the world’s first CRISPR edited babies were ‘created’ in China
What happened to the CRISPR babies?
At this point, I was curious to know what is the latest on the CRISPR babies (now 3 years old). A quick recap on this below.
In Nov 2018 biophysicist He Jiankui created the world’s first designer babies ‘twin girls’ (Lula and Nana) in China through genes edited with CRISPR to make them immune to HIV. The father was HIV positive while the mother was not.
This invariably provoked an international outcry with shock and outrage among scientists worldwide (CRISPR's founder dubbed it horrifying!). Scientists felt that years of research are needed to show that meddling with the genome of an embryo causes no harm. This step was condemned as premature, dangerous, and irresponsible. The experiment itself was full of technical errors and ethical blunders.
In Dec 2019, He Jiankui was jailed for three years by the Chinese Govt. as he violated a Govt. ban to carry out experiments on human embryos.
As for the twins, both are being monitored until they turn 18. The children had virtually no risk of contracting HIV. So even if the experiment is successful there is no way to infer whether it conferred any benefit (so much for the effort and public ire He Jiankui!)
What is CRISPR’s potential and the legitimate concerns?
CRISPR can be used in both drug discovery and therapeutic treatments and has three main applications. First is the ability to manipulate genes to turn them on or off within people. The most promising application in this is to modify the monogenetic diseases (7K+) that can be traced back to a single gene that has a defect.
The second is to create medications that can be infused- taking blood and certain cells out of a body, manipulating them with CRISPR, and putting them back in.
The third is in farming. CRISPR is being used to create enhanced foods (corn resistant to herbicide or grapes that are freeze-resistant) or to create better-tasting foods.
In 2017, for the first time, CRISPR was used to repair a genetic mutation that could cause a heart defect.
And to extend its application, what if organisms that are value destructive for the environment such as locusts, termites, etc. could be wiped out from the face of Earth?
In an interesting use case from the series, in Sep 2019, researchers led a project called Target Malaria in Burkina Faso (malaria capital of the world) and released 10K genetically modified sterile male mosquitoes in a small village. The intent of the controversial experiment was to wipe out the female mosquitoes who are carriers of the disease.
While this could mitigate the problem, the second-order effects of genetically modifying an organism and releasing it into the wild are something that even scientists are apprehensive and cautious towards.
At the worst, it can lead to an ecological and eugenics collapse (the practice to improve human species by selectively mating people with specific desirable hereditary traits). Unexpected mutations can have consequences that lead to profound and dangerous implications for the environment.
This brings us to some legitimate concerns to be addressed with CRISPR
CRISPR has prompted both breathless predictions of medical breakthroughs and warnings of an apocalypse! As John Oliver quipped, ‘it seems gene editing is going to eliminate all disease or kill every last one of us’.
And as Spiderman’s uncle states, ‘With great power comes great responsibility. But are we yet equipped to handle the enormous responsibility bestowed by CRISPR?
The risk of a poorly regulated clinical trial is enormous. A single tragic death in experiments can probably set back the field of gene therapies by a decade.
Citing the designer babies experiment in 2018 in China, things might not go as planned or have unintended negative consequences. The first few patients are going to be the ‘guinea pigs’ considering there is little scientific evidence or experimentation results available for most of these technologies.
In one of the episodes, New Zealand is suffering from a rodent boom due to climate change that can threaten its native bird population. Dr. Kevin Esvelt, an evolutionary engineer used a process called gene drive in rodents to control their breeding. Gene drive is a new risky technology where the goal is to drive a single trait through a population or species for generations to come.
Owing to the huge public outcry, the current NZ Govt. stopped all funding of gene drive technologies and is pursuing other methods to achieve a predator-free NZ by 2050.
Dr. Kevin remains resolute though and received the first approval to release genetically modified mice in Massachusetts in 2019 to stop Lyme disease although concerns remain.
On the pricing part, another big concern is that these drugs are super expensive at present and pharma companies are reaping profits from these miracle drugs. For a drug that treats muscular atrophy, the cost is $750K for the first year and then $350K for life. Luxturna which treats hereditary degeneration of the retina is priced at $850K for a one-time treatment and is among the world’s most expensive drugs.
Then there is the concern for ‘desperate patients’ who seek treatments at any cost and might resort to spurious clinics that inflict more harm than recovery. In Dec 2017, the American Society for Gene and Cell Therapy issued a statement warning patients about unregulated gene therapies and said that such procedures are potentially dangerous and unlikely to provide any benefit.
Proper awareness and necessary regulations to crack down on unverified clinics and centers is critical to avoid patients being swayed by such promises. Granting IPR for gene editing tools could also be an option.
CRISPR requires patience and years of research. Recent studies suggest that while CRISPR can cause cells to lose their cancer-fighting ability, it can do more damage to the genes than previously understood. Scientists need to proceed with utmost caution and check for possible harmful effects.
Lastly, the biggest fear is of humans manipulating the genetic code (intended biowarfare or unintended slip) and those manipulations get passed on from generation to generation. The changes can lead to antibiotic resistance or other mutations that go into the population and become very difficult to control.
To take an analogy you might intend to edit one letter of the book of life, but actually, alter entire pages of the book in unintended areas (something that happened with the designer babies).
Apart from these concerns, there are moral and ethical implications too.
There are some fundamental issues to address in terms of who controls the technology and has the power to accept/ reject advancements, who is profiting and how do big tech, powerful corporations with enormous control and lobbying power think about their involvement.
Secondly, biohacker’s ‘noble’ aim is to democratize science but what if their discoveries are not evenly distributed across the population? What if instead of making significant advancements to humanity, they actually exacerbate social inequality where the rich get access to miracle cures and designer babies through their technologies?
Lastly, there is always a lingering fear of ‘trying something new’ and its repercussions. To cite an example, IVF or test-tube babies were considered unnatural with no soul when it was first launched. Over the years, it has achieved mainstream acceptance.
Due to all these concerns, scientists in the US have called for a self-imposed ethical moratorium on CRISPR until more is known particularly for germline mutations. In Jun 2019, US Congress voted to uphold the ban on creating genetically modified babies despite calls from a few scientists to lift the ban and allow FDA to review its application for new technologies.
But work in other fields and its varied applications continue.
Recent innovations
In Dec 2017, the US approved the first gene therapy for an inherited form of vision loss and approved Luxturna from Spark Therapeutics for commercial use (as an aside there is a story of a young boy in the series who takes this drug to significantly improve his vision which is a delightful watch!).
Already a bunch of pharma and drug companies have done gene-editing innovations. GSK’s Strimvelis which provides a cure for fatal immune deficiency is approved in Europe, Novartis drug Kymriah has been approved in the US to edit cancer-fighting genes in children with leukemia. AveXi, a gene therapy company in Illinois focuses on spinal muscular atrophy.
In Apr 2021, researchers at Weismann Lab developed a new technology called CRISPR on and CRISPRoff that targets specific genes and turns them on or off without changing their DNA code.
In the series, the last episode talks about the concept of a ‘three-parent baby’ IVF. It shows a couple from Ukraine who successfully used this. In this mechanism, a small amount of faulty DNA (mitochondrial gene) in the mother’s egg is replaced with healthy DNA from a second woman. The baby inherits genes from two mothers and one father. The intent is to prohibit certain genetic diseases to be passed on to the children or allow women who can’t give birth to use this. The idea is still controversial and three-parent IVF is banned in the USA.
For readers keen to read more on the latest breakthroughs with CRISPR, here is a year in review update of 2019, 2020, and 2021 (pretty comprehensive!)
What does the future hold?
Most of the microbiologists, biochemists, geneticists, ecologists, and doctors in the series are ambivalent and quite conscious of the choice of their actions and of the unintended repercussions.
In the future, societal pressures can force individuals to alter their or their kid’s biology even if they don’t want to. Remaining merely ‘human’ in a world of superhumans could become increasingly hard. One could also face professional discrimination or moral condemnation for the choice to remain ‘suboptimal’ when most humans can level up.
At a practical level, it also looks impossible to distribute the benefits of gene editing technologies equitably across the world when even access to health insurance is not widespread.
Unintended experiments could also run aground to produce new species that are more intelligent, stronger, and unstoppable which could threaten the existence of mankind itself. As Dr. Esvelt remarks, “The prospect of a wave of genetically modified anything sweeping generation after generation, geographically expanding into city, country, across continents, is utterly terrifying.”
The societal and environmental implications of the technology are huge and hence it must be carefully controlled and supervised.
There are also powerful forces in play here and organizations with immense lobbying power who want to use these technologies for their own benefits and as quickly as possible. For instance, agribusiness and chemical companies are interested because it allows them to ‘control’ nature.
Overall, as a society, it’s extremely important to understand this technology, discuss it and not leave the choice to make decisions only with people in the lab or with the power to decide its future course.
The ethics of gene editing should be openly discussed and regulations in the space need to catch up. Discussion could include topics like- Is it ethical to edit your child’s DNA or your own? Is the answer influenced by whether you have a degenerative disease or your child has the rarest defect of vision loss?
Ultimately if the technology can help a kid get his/ her vision back or prevent people in Burkina Faso to suffer from a horrible disease like malaria, it makes sense to think of ways where it can be selectively used to make advancements in mankind and for further scientific innovation.
Who would say no to a world where no kid is born without any genetic disease ever!
As an overarching rule, if it is a sickening, life-threatening disease you can edit it out. But if it is an enhancement that helps improve your physical/ mental capacities or a memory gene that allows you to think better, that should remain out of bounds.
The public also largely concurs with this. In Dec 2017, Nuffield Council on Bioethics (London-based independent advisory committee) published a survey where 70% supported gene editing for infertile couples to have children or allow couples to alter a disease-causing mutation in an embryo.
On the positive side, the revolutionary impact of the technology on new cancer therapies or to cure inherited diseases is truly remarkable. CRISPR has allowed plant researchers to develop crops that can withstand mold, pests, and drought. The magic of RNA gave use the first C-19 vaccines which were produced in a record-breaking time of a year when vaccine development has usually taken 3–4 years. The genetic scissors have allowed life sciences and humankind to progress in the best possible manner which is a celebratory feat itself.
Overall genetic editing is here. Startups, scientists, technologists behind the therapies, and new discoveries are moving fast especially after the pandemic. CRISPR-based platforms have altered molecular biology and are poised to redefine the practice of medicine in the next phase.
As Siddhartha Mukherjee mentions, the Industrial Revolution was a revolution of the atom, the IT and internet revolution was of the byte. The next revolution underway is of the genes which remodel life.
And this will be the most fundamental revolution that reimagines and alters humanity itself!
Additional Reads
For a read on CRISPR and its evolution
The Human Genome Project to map and understand all the genes of human beings
Designer Babies in India: Where should we draw the line?
Realizing the potential of CRISPR
The views and opinions expressed in this article are those of the author and do not necessarily reflect those of any institute or organization he is or was previously associated with.
