With A Possibility For CRISPR To Cure “All” Diseases, Should All New Biotech Companies Be Designated Public Benefit Corporations (PBCs) To Thwart Potentially Specious Big Pharma Takeovers?

With A Possibility For CRISPR To Cure “All” Diseases, Should All New Biotech Companies Be Designated Public Benefit Corporations (PBCs) To Thwart Potentially Specious Big Pharma Takeovers?

A neoteric philosophy on CRISPR (Cas9 and other variants): biotech startups; takeovers; Big Pharma (potentially comprised with executives susceptible to unscrupulous profit motives); a designate known as 'PBC'; and China.

It was not just another discovery—it was a gift from the gods of Promethean grandeur.  When discovered, CRISPR—acronymic of Clustered Regularly Interspaced Short Palindromic Repeats—descended onto humanity a wieldy and powerful tool.  Since then, CRISPR has shown a biotechnical ability in gene-edting that was entirely unique and unknown to the sciences.  It showed capabilities that could combat disease with a strategy that involved precision while also being deemed safe, although the latter is yet to be thoroughly proven. 

Doomsday scenarioists say that CRISPR has the potential to place extreme harm on a grand scale.  They’re not wrong.  Jennifer Doudna, one of CRISPR’s (Cas9) co-inventors, has also expressed similar concern.  When asked in an interview, Doudna also cites a nightmare she had: in Doudna’s dream she was approached by Hitler asking about the gene-editing tool—a technology that correlates in principal with eugenics.  As CRISPR alters genetic code it has the ability to alter the germline, the molecular cluster that passes on to progeny—one of its few longterm, permanent effects.  

There are other issues that CRISPR can also be used as a weapon of mass destruction by synthesizing viruses in a lab that might aim at gene-specific targets, namely those in humans.  Ethical concerns are undoubtedly an issue.  There is no dispute in the potential for catastrophe, but the CRISPR genie, they say, is already out of the vial; however, no other technology has the potential to bring so much incontrovertible good to humanity and to those suffering in the shadows.

There is no dispute in the potential for catastrophe, but the CRISPR genie, they say, is already out of the vial; however, no other technology has the potential to bring so much incontrovertible good to humanity and to those suffering in the shadows.

CRISPR offers a new approach to medicine.  In its ability to seek DNA with specificity, and taking misguided guessing out of the hunt, it will ultimately change the biosciences, medicine, if not humanity, forever.  This kind of potential is a boon but then it’s also a bust for those involved in for-profit production of medicine and/or treatments.   

To treat or to find cures for diseases, in part, involves some guessing, often times incorporating a lot of trial and error, experiments that become arduous, ineffective, time-consuming and ultimately costly; and in some cases, deadly.  It’s no wonder that some methods are frustrating and why cures in general have been so elusive to scientists (with FDA roadblocks and/or lack of funding also contributing to the list of potential pitfalls).    

Traditional vaccines can take over a decade if not longer to develop in non-pandemic circumstances.  Functionally curative vaccines are notoriously difficult to make safe, effective and available to market; they are sometimes only prophylactic in nature, and can face protractively long regulatory hurdles. 

With 2019-nCoV (aka Covid-19), the international scientific community are now working tirelessly and collaboratively to find a vaccine.  The general consensus for a realistic timeline to develop a 2019-nCoV vaccine is somewhere around 18 months; but some are suggesting there could be a vaccine inside of a year utilizing a new technology called mRNA.  An mRNA vaccine is considered faster and cheaper to develop, while also not using a part of the virus in the way conventional vaccines historically do. 

Like mRNA, new technologies in the biosciences are ready to disrupt the pharmaceutical industry.  However, while millions currently suffer, many cures supposedly already exist as skimmed potential of underdeveloped research.  

To give one brief example, co-founder, CEO and now medical pioneer Martine Rothblatt, discovered a curative treatment for her ailing daughter, who—prior to Rothblatt’s involvement—suffered from a rare and fatal pulmonary disorder.  

To be more specific, it was a cure-in-waiting, one already discovered in theoretical, scientific research but never having reached human trials: the cure, essentially R&D that sat on a shelf at GlaxoSmithKline, was never developed because it wasn’t deemed cost effective for the company; i.e. because of the rarity of the disease, the life-saving treatment was never pursued as the overall cost to develop it would exceed any potential profit.  

Instead, Rothblatt on her own accord and with her company, developed and brought to market the drug that saved the life of her daughter and ultimately thousands of others.  The exclamation point to this story is that Rothblatt’s company maintains a policy to make this life-saving drug available to all who can’t afford it.  Imagine, if one will, more stories like this pervading social media threads.  

Some say that cases of undeveloped cures waiting to have the dust blown off their research files are supposedly common in the industry, i.e. the costs to make them financially viable prevent them from ever reaching the market.  Let that sink in for a moment.  No “cure” is assured, there are risks, and those risks are mostly a financial gamble.  In terms of available resources for any given company, we know this ostensibly makes sense, even logical sense, but ethically, it feels void of humanity.  If it weren’t for the independent motivations of Rothblatt and her pool of resources, many would still be dying tragically.  Less of a gamble, her actions were derived from benevolent necessity, than a concern for profit or financial loss.

For something that should be made available to the global population, a country is seeking exclusive rights to a cure.  If a president and his administration are willing to make this kind of manoeuvre in the open, imagine what Big Pharma would be willing to do behind closed doors.   

If humanitarian initiatives are left to the individual, the system, it seems, is dysfunctional if not broken.  Something has to change.  At the very least, greater transparency is needed if supposed cures continue to collect dust on shelves so that those who can make a difference are at least aware of their existance, and, moreover, can push to make them available to those who need it.      

For those who think that the following might have the stigmatizing tinge of conspiracy theory, it should be noted that the president of the United States recently offered German company, Curevac, a billion dollars for the exclusive rights to a coronavirus vaccine.  This offer has been described by some as a ‘takeover’.  For something that should be made available to the global population, a country is seeking exclusive rights to a cure.  If a president and his administration are willing to make this kind of manoeuvre in the open, imagine what Big Pharma would be willing to do behind closed doors.

Say what you will about the benefits of capitalism and the free market, the ethical discussion is a slippery slope when it comes to healthcare: there’s a fine line between expediting bottomlines and expediting cures; cures that could substantially save billions in healthcare costs while improving lives or saving them.  The positive economic effect as well as the humanitarian benefit would reverberate, swinging in the opposite pendulum of what is seen in the current Covid-19 trend of economic recession, if not depression.  

Think of it as a collective antibody to economic stresses that will liberate millions to prosperity.  That’s in addition to all the rumblings of an aging population and its drain on society long seen as a tsunami on the horizon, while countless others are shackled by their current afflictions, including mental as well as physical maladies.

The world wants and needs affordable health-care (even for countries who already have it) and above all—cures.  

Enter CRISPR. 

crispr_PBC copy

CRISPR has been touted as cheap and accurate with promises of efficacy.  ‘Cheap’ and ‘effective’ medicine are two words the public want to hear.  Conversely, they are not the words that Big Pharma ever wants to hear if what is cheap and effective isn’t under their ownership.  

For politicians seeking ways to restructure or overhaul current healthcare systems that put millions at risk—burdened by costs, an aging population, by unscrupulous agents (e.g. Martin Shkreli), or the coming tsunami of generations unable to save for age-related maladies—CRISPR could be the necessary disruptor for many of these issues.  

If so, biotech companies pursuing cures with CRISPR-Cas9 and other Cas variants, should in some way be protected, out of reach from unscrupulous agents hoping to see them fail.  Despite being supposedly cheap, CRISPR research is still costly, with companies needing substantial financial investment.  And because profit-motives still underpin a company’s course of action, exacerbated by market pressures including shareholder expectations, company’s can become vulnerable to these pressures and thus susceptible to takeovers.    

One precautionary tool for any potentially unscrupulous activity or takeover could be something called a Public Benefit Corporation (PBC).  It is not a common designate for corporations, but in medicine—as Martine Rothblatt has employed for her corporation Lung Biotechnology—it has the ability to protect a company’s core values and its R&D.  As part of a PBC, the company’s board can prevent hostile takeovers from companies whose profit-driven mission might not align with that of the founding members, protecting what is ultimately a benefit to the public just as it is for the company.

There are many large corporate entities that have or continue to operate as PBCs, including one of Canada’s more historic and storied companies: Hudson’s Bay Company (founded in 1670, is North America’s oldest company, although it’s unclear if it’s still a PBC).  Many other Public Benefit Corporations include transportation and aviation authorities in the U.S.  If being a PBC seems to be an obvious choice for these companies then perhaps a marriage with the entirety of the biotech community could be as well.  

Don’t let the ‘Public Benefit’ portion alter the perception of the title as anti-capitalist in nature.  PBCs still operate as any corporation looking to maximize profits, with the ultimate caveat being that any decision can be vetoed if deemed by the company’s board members as inappropriate, unethical or deviating from the original course of its drug and curative research.  No model is perfect, but without board members in attendance to such transactions while the rest of us go on living blithely, there are obvious risks no matter how cynical they might come across in an imagined scenario.  

Picture, for example, a small medical startup losing its source of capital or it hits roadblocks due to unforeseen trials, leading to the lure of a takeover.  If one private (or public) company flounders, is sold by its head or by its board members enticed by a proposal from a larger pharmaceutical company, with it will go patents and all the accumulated research devoted to a specific cure.  It’s conceivable that research gets “temporarily” shelved for other initiatives, is set aside due to restructuring, and/or that same research is stultified and altered from possible “cure” to a probable “treatment” as a more lucrative executive decision.  And when it comes to Big Pharma, lucrative executive decisions are centred around the company’s best interests, not the public’s-

Recently, as part of a re-submission application, Intarcia Therapeutics lost FDA approval for its revolutionary implantable type-2 diabetes treatment.  It’s unknown what will happen to the company if it continues on this path of rejection, or if it has resources to sustain regulatory roadblocks.  What would happen if investors walk away and R&D efforts are halted?  It’s plausible that Intarcia’s new treatment will never see the light of day, or to continue their mission they might have to sell at the mercy of their giant competitors.

Big Pharma, having vaulted the cost of insulin in the U.S., understands that this life-saving drug (invented by Canadians Banting, Collip and Best whose patent was sold for $1 to the University of Toronto) perpetually feeds its bottomlines into the billions, while the afflicted pay, or worse, skip dosages due to high costs.  

To ignore stories like this is to create a dangerous blind-spot.  With potential CRISPR cures—the kind that undercut for-profit pharmaceutical companies reliant on steady streams of revenue from their existing production of drugs to offset costs of new and old research/clinical trials–CRISPR R&D will not only see threats from potential buyouts, but FDA regulatory hurdles could stifle progress as well.

[Other recent advances can also be included under the same umbrella of revolutionary technologies, e.g. stem cells or drugs designed with advanced, AI-driven protein folds, like that developed by ProteinQure.  Despite protein-folding traditionally being a cost-hindering technique, recent advances in computational processing—namely in quantum computing—have made it largely feasible.]

With any potential change, it can often make many very uncomfortable, particularly those who stand to lose.  With seismic change, dynamics of power invariably also change and the extent to which some entities exercise their power can become unpredictable.

Some of the Titans of Big Pharma; the global revenue of the pharmaceutical industry was approximately $1.2 trillion (USD) in 2018, and is quickly approaching 1.5 trillion. (source Statista)

As new biotech sweeps in, the impetus for this article is less about CRISPR’s science and more about overarching ethical concerns.  In the era of distractions, it is easy to overlook the truly consequential problems that take place behind the scenes of our collective quotidian lives.  The looming U.S. election overpowers and limits our field of view with endless distractions.  So do annual festivals, COVID-19, online entertainment, the start of baseball season; and while many think the next electoral win is pivotal in preventing eschatological outcomes, it might be just as prudent to keep a watchful eye on giant corporations positioning themselves to deal with CRISPR as it moves in to siphon their bottomlines.  

Disruptive, existential threats to companies by way of new (and forgotten) technology have a way of making executives nervous.  This can be seen with current auto manufacturers who are anticipating a decline in auto sales and in their offshoot businesses including financing, and dealership services.

Not only can some electric cars out perform ICE vehicles, they are less costly to maintain, and in time, they will be cheaper.  Disruptors are naturally positioned to be ‘cheaper’ and more ‘effective’ than their competitors.  

Consider the potential for a peptide based biogenic dental product, which, if it does reach market, will be an over-the-counter product able to repair and heal cavities.  Count on it to shrink the incomes of dentists and the overall lucrative profession of dentistry.  A ‘cheap’ over-the-counter product that’s ‘effective’ will not be welcomed by all.  Anticipate pushback from any industry unable to adapt, where technology swarms in to better consumers at the expense of corporate competitors.

Private companies, like any living organism will do anything to survive.  Big Pharma, too, will find ways to maintain their dominance.  A CEO of a major pharmaceutical would naturally want to stymie products that are cheaper and more effective than the products their company produces from coming to market.  It might mean buying out smaller competitive startups in need of seed-funding, when resources erode after years of clinical trials.

It’s difficult to avoid the stain of being called a cynic on this topic, but to clarify, this is not about any conspiracy per se, this is to bring caution to the fore.  This is a clarion call to the masses, and to those who can make a difference, who can keep vigilant on such matters.  

If no one else will, it is ultimately up to private corporate entities to prevent any dubios takeovers, to act as safeguards to their research.  However, the simplest tool could be to register business(es) as Public Benefit Corporations (PBC).  It can’t be stressed enough, that by doing so, any potential takeover can be prevented if the PBC board feels the intentions of the overtaking entity are impure.

CRISPR as a means to fight inequality: For countries where millions are uninsured, "cheap" and "effective" CRISPR as a method to curing and preventing disease could be an answer to disrupting the financial structures that anchor current healthcare systems.

If current healthcare systems are prevented changes that are arguably needed, then CRISPR could be a tool to circumvent the current pharmaceutical industrial complex. The medical lobby in the U.S. by some considerable measure is larger and more powerful than the gun lobby.  Yet, it’s rarely discussed from this angle.  

Any significant changes to healthcare is simply deemed ‘communist’, while comparisons to free healthcare systems around the world and their supposed inefficiencies are assiduously scattered and sowed in the media.  

Let’s not forget the effects Big Pharma has had on the opioid crisis, through unconscionable malpractice and neglectful inefficiencies that were entirely preventable.  The current system can put many U.S. citizens into financial destitution; after decades of working and saving, many see an unexpected health event drain it all.  This isn’t unfortunate, it’s tragic.  

And yet, outside the opioid crisis, how many more die or suffer needlessly?  If democracy can’t change the system, then perhaps new technology can.  But that technology should be protected and shared so as to prevent corruption.  

It isn’t just U.S. citizens who can directly benefit from cheap and effective technology in the health sciences.  Imagine a biotech cure for blindness, researched and developed in the West, finding its way to the most forgotten parts of the world (areas where a certain political culture breeds hate towards the West), and what universal common good that would avail itself.  A mother—whose child is born with congenital blindness finds that her child’s CRISPR cure was developed in the United States—would perhaps see the world differently.   

Forgive the sentimental idealism here and in most of this piece, but CRISPR benefits are incalculable and why CRISPR startups must be protected because their value isn’t solely financial, it’s broadly societal and humanitarian in scope

China:  Fierce International Competition In Biotech Breeds New Possibilities 

CRISPR, in a sense, has ushered in a Cold War of scientific research between China and the rest of the world.  The stakes are high as China’s advantage is its industrial and human resources, including a pool of talented, educated scientists anxiously willing to make their historic mark, and in some cases, crossing ethical boundaries to make them.  

Take for example, Dr. He Jiankui, who in 2018 eagerly CRISPR-ed twin babies, engineering them to be impervious to HIV by turning off a protein called CCR—among other genetic alterations—in a world first.  Dr. Jiankui was unanimously condemned by the international scientific community for his action, and was later sentenced to prison in 2019 for his premature and ultimately dangerous decision for a technology still largely unproven to be safe.  

Still, it is worth noting that one scientist took it upon himself to bioengineer in what is largely still an unproven landscape of genetic science.  But, the science is here, and its approval by regulatory bodies is nigh.  

Recently, the first human trials of CRISPR in the U.S. were concluded and the process was deemed safe though ineffective in curing the cancer they were treating.  By comparison, China is currently conducting over a hundred human trials (while also having built the world’s largest DNA database some years ago), and appear light years ahead of the U.S., and are poised to dominate research, the speed toward human trials, and likely CRISPR “approvals”.    

China To The Rescue? 

More importantly, China not only appears light years ahead of the U.S. in CRISPR initiatives, it is miles upon miles from Big Pharma’s reach (and the FDA).  China’s interests will not be hindered by FDA regulations, although assumedly they will be complying within international guidelines and standards to substantiate their research.  It’s entirely in their best interest to be peer-reviewed in lauded journals so as to maintain credibility to market abroad—to those seeking a CRISPR treatment or cure.  

China’s CRISPR initiatives won’t likely face financial shortfalls either, if the government has anything to say about it.  It is also highly unlikely that Big Pharma would be able to acquire any of the Chinese projects, many of which are backed by the government. 

In a way, China acts as a safeguard for the rest of the world as it holds its personal interests in CRISPR technology.  This allows for competition between the world’s two largest economies, giants trying to out compete the other in treaments and IND applications, but ultimately, the first to a cure, will win. Whatever cures Chinese scientists find will also bypass the sometimes strenuous and prolonged scrutiny of the FDA, which means they’ll first to reach the curative finishline, with rows of patients waiting to see it crossed sooner rather than later.  

To be first in this regard would mean having to aim at a cure rather than a treatment, because one’s profits could be easily lost if a competitor storms in with a CRISPR cure, which CRISPR is often said to have the potential of doing.  This should force the FDA to make changes to speed up processes if they don’t want to see millions of Americans flying to China for treatments and cures.  There’s little patience for ailments and suffering, and many are willing to risk their health for the mere potential to permanently improve their well-being.

At a time when China is taking a lot of criticism for Covid-19, it might well be that China is a saving grace for the future of medicine, and that competition between two giants may indeed create a tsunami of innovation that cannot be capped by spurious entities.  

The threat CRISPR poses to large pharmaceutical companies and their bottomlines is undeniable; CRISPR is a disruptor, and executives are intelligent enough to register the threat and they’ll be vigilant in stopping the dangers to their overall operations.  When executives of any industry are posed with a threat, one strategy is to acquire the threat and to squash it.  Why wouldn’t giant pharmaceutical companies do the same?

CRISPR as open source bio-software?

Since CRISPR will be highly sought after for its potential to cure anything, it opens a potential black market for rogue entities.  This scenario is less plausible; however, bet on an underground market to become a reality if authorities do not make CRISPR’s potential accessible to the masses.  

It’s conceivable that there might be a time when unseasoned CRISPR scientists experiment in the thousands, like coders creating apps; manipulating open source CRISPR to create bio-apps, later droned to one’s front door, or prepackaged and sold in a shadowy alley.  Currently, there are CRISPR DIY kits to start CRISPR-cutting at home. 

A scientist and “biohacker” named Josiah Zayner made headlines as an advocate for DIY genetic adjusting.  Zayner administered CRISPR on himself with at-home CRISPR kits, even posting videos of his experiments noting how easy it was to do.  

It’s well-known that CRISPR kits are available online, although yet to be proven safe outside any accredited laboratory (if ever) this is how easily accessible the genetic manipulator is for any garage lab technician to administer. 

In a far-off future, CRISPR may become an independent, sharable, Tor-browsing, back-alley technology that will offer potential cures or treatments.  Many desperately ill will take any  measures despite regulatory barriers or warnings especially if it’s affordable.  If biotech startups fail or fall short of funding to complete FDA approval, or if they’re taken over by Big Pharma looking to profit in treating disease in lieu of curing them, perhaps an underground market will emerge to counter any financial malfeasance or otherwise unscrupulous activity.  

While there is no sense of urgency at present for underground CRISPR markets, perhaps an alternative strategy is to see all new private biotech companies register as Public Benefit Corporations.  The phrase ‘public benefit’ can evoke anti-competitive, socialist tones to those looking to find fault, but the model doesn’t hinder progress; it simply allows for a board of its original founders/members to veto executive decisions that might prove threatening to the overall research and mission of the company.   

It keeps all new interested buyers and members in line with the original objectives of the research, i.e., if the original goal is to cure a disease, that objective still remains, while opposing more profit-driven motives like attenuated perpetual treatments.  

It is objectionable to see the number of prescription drug commercials that flood U.S. airwaves.  There are so many competing interests for advertising air time from Big Pharma it’s no wonder they need to raise prices on drugs.  There’s a great imbalance here, and the model has to change somewhere.  The Canadian model has its soft spots, but Banting made an ethical decision to protect those in need of a life-saving drug.  $1 covered Banting’s coffee that monumental day in exchange for lives saved and peace of mind.  Knowing that CRISPR cures are imminent, who or what will protect the public from potentially unconscionable executive decisions.  It might not be a solution, but merely registering one’s biotech company as a PBC could be the peace of mind we all need.