Gene Editing: The Devil’s in the DNA
SCENARIO: The Verde avocado was one of several fruits introduced by biotech pioneer AgriBoundless. The Verde was a biotech success story — a genetically edited variety with flesh that was very slow to brown after cutting.
Restaurants and other establishments across the food service spectrum gave Verde the thumbs-up for helping to cut down waste caused by the short shelf-life of avocados — a popular but costly ingredient. National Tex-Mex chain Meximillion was the largest purchaser of Verde, ordering them chain-wide after a brief trial in numerous California locations.
Nearly a year after its introduction, however, a paper published by UC San Diego School of Medicine’s immunology division traced a series of mysterious allergy cases back to the Verde avocado.
Only a small percentage of people developed an allergy to the Verde avocado, but it was enough for a sizable class action.
The paper sparked a flurry of interest from immunologists across the country grappling with similar cases.
Agriculture officials ordered a recall of Verde, pending an investigation. Meximillion and other establishments struggled to secure alternate suppliers. Restaurants in some regions had to take guacamole and other popular items off of their menus.
The investigation wasn’t yet complete when the lawyers came knocking. Only a small percentage of people developed an allergy to the Verde avocado, but it was enough for a sizable class action.
A few of the affected consumers, including one child, nearly went into anaphylactic shock. AgriBoundless and its distributors were named in the suit, as well as Meximillion and four other restaurant chains.
Long before the case ever got to trial, Meximillion was tried and found guilty in the court of public opinion for putting genetically edited food on its menu. Its actions conflicted with its brand, which was wrapped around its fresh and natural ingredients and its “No to GMO” stance.
A crisis management team immediately launched an educational campaign to help people understand that the Verde avocado was non-GMO, but the public presumed that even if it wasn’t GMO, it had to be just as bad.
Competitors were eager to let their customers know that they only used “real” avocados.
The next meeting of Meximillion’s shareholders was a grim one indeed.
ANALYSIS: In a 1923 essay, scientist J. B. S. Haldane imagined the invention of a purple alga called Porphyrococcus, which so accelerated wheat yields that it led to a food glut, virtually collapsing the economy of agricultural states.
In Haldane’s scenario, an errant strain of the algae escaped into the ocean and multiplied, creating so many nutrients that it resulted in an explosion of the fish population.
Oh, by the way, it also turned the ocean purple, permanently.
Haldane was ahead of his time, yet no prophet … the Atlantic remains blue. But just shy of a century later, the science that Haldane imagined is our reality.
New organisms like Haldane’s purple algae are being created from scratch by mankind rather than Mother Nature. And mankind is taking nature’s existing creations and altering their genetic structure to better suit our needs. Thanks to recent advances, these feats can be accomplished with stunning speed and at less cost than ever before.
The discovery of a system known as Crispr-Cas9 is a massive lunge forward in biotechnology. Crispr-Cas9 is a like a DNA scissor — a genetic equivalent of the find and replace function of a word processor. It gives scientists the ability to delete or swap out pieces of a genome in order to change or eliminate traits.
A snip here, a snip there and voila — two bulls born recently in Iowa will never grow horns. Neither will their offspring. What used to take many generations to accomplish via selective breeding can be achieved in just one, with more precision.
Crispr-Cas9 is also a game-changer because it makes genome editing accessible to an unprecedented degree. An edited genome can now be produced in a matter of days. And the process is so straightforward that a grad student can master it in about hour, say scientists.
UC Berkeley biochemist Jennifer Doudna explains what Crispr-Cas9 is and what researchers hope to accomplish with it.
The possibility for advances in medicine and pharmaceuticals is breathtaking. Scientists are hard at work on projects such as engineering cancer patients’ immune cells to more effectively attack tumors.
A company called Intrexon may be on the verge of editing out the ability to transmit the Zika virus in the wild mosquito population.
Man-made yeasts and algae are being tested to produce everything from new biofuels to cosmetic oils to “natural” vanilla flavoring.
Synthetic yeasts in development are being tested for their ability to change the flavor of yogurt, bread, beer and pickles. Gene editing is being tested for its ability to edit fruits and vegetables to increase their edible flesh, resist browning and retard ripening.
“We, as responsible members of the risk management community, want to encourage a balance. We want to encourage innovation.”— Walker Taylor, managing director, life sciences practice, Arthur J. Gallagher & Co.
Gene-editing research on animals is yielding stunning results. Scientists produced pigs that are easier to fatten up, cattle that produce more tender meat (and more of it), cashmere goats that grow longer hair, and chickens that produce only female offspring for egg-laying, among many other apparently successful improvements upon what nature created.
Keep in mind that the first synthetic genome was created in 2010, and Crispr-Cas9’s true potential came to the fore just two years later — these breakthroughs haven’t even scratched the surface of what may come.
Debates and hand-wringing are in full swing over human genome editing as well as the potential bioweapon applications of gene editing and synthetic biology (synbio). But threats related to commercial applications are no less controversial, from the possible effects on human health to concerns about the environment and biodiversity.
“We would expect such products to be thoroughly tested at every stage of their development,” said an insurance executive, “but there are no guarantees — you can never completely eliminate the risk that they might interact with the wider environment in unexpected ways.”
A complex regulatory environment is expected to keep the risk level in check for medical and pharmaceutical industries. But the regulation of agricultural and food products is a very different process.
“Remember Olestra? They put it out in the food chain and then went, ‘Whoa! This is not good for our bodies.’ ”— Sandie S. Mullen, senior vice president, national life science practice leader, RT Specialty
Established regulatory environments do address biotechnology products. From a risk management standpoint, experts noted it should be reassuring to insurers and others that these technologies “are not operating in a regulatory vacuum.”
There are subtleties still to be sorted out, however. While an edited genome is modified, it is not currently considered GMO. That distinction is reserved for organisms with foreign DNA added to their own. Edited genes contain no foreign DNA. The result is the same species, just altered somewhat.
Current regulatory structures don’t address this kind of modification, so edited genomes are not subject to the more stringent approval process that governs GMOs. The U.S. Department of Agriculture is studying Crispr-Cas9 and plans to make recommendations in the near future.
In the meantime, seemingly benign products of biotechnology will quietly work their way through the agricultural and manufacturing sectors, into our homes and businesses as well as onto our plates. If there are problems, they will eventually make themselves known.
“Remember Olestra?” asked Sandie S. Mullen, senior vice president, national life science practice leader with RT Specialty. “They put it out in the food chain and then went, ‘Whoa! This is not good for our bodies.’ ”
As long as a product is deemed generally safe for the public, it’s going to be sold.
“If you come up with a new vanilla or a new oil, you can put it out in the marketplace. And if it doesn’t immediately cause [harm], it could be out in the marketplace for years,” said Mullen, also citing asbestos as an obvious example of how significant hazards can lurk in the shadows.
Current regulations, however, could soon change the way companies weigh the use of biotech products in their own operations.
In July of 2015, the White House directed the EPA, FDA and USDA to overhaul the federal Coordinated Framework for Regulation of Biotechnology, which has not been updated since 1992. As part of that directive, the agencies were to develop a strategy “to ensure that the federal regulatory system is well-equipped to assess efficiently any risks associated with the future products of biotechnology.” The first public meeting on the update was held this past October.
For now, products created through synthetic biology or gene editing technology are considered distinct from GMOs and don’t need to be labeled as such, allowing manufacturers to avoid association with the GMO stigma that has been created by the media and certain public interest groups.
But the lack of transparency could eventually backfire, as in our avocado scenario. If the information is made public unexpectedly, the potential for reputational risk can be quite severe.
Insurers’ Key Role
Though in its infancy, this science has the attention of numerous industries. This presents some thorny challenges for risk managers and insurers. Risk managers will need to weigh the specific benefits of biotech products against their potential risks — no easy feat when the risks are largely unknown.
In gene editing, the problem of “off-target mutations” is well established. Scientists are already making strides in reducing these mutations, but there’s no ironclad guarantee that some latent mutation won’t produce an unforeseen effect down the road.
Switching to a biotech ingredient could yield significant cost savings, but companies must be open to discussing the possible latent issues that might arise with brokers and carriers.
“We’re talking about risks that are low frequency, high severity — I think this industry presents a lot of that,” said Walker Taylor, area president and managing director of the life sciences practice at Arthur J. Gallagher & Co.
“It makes good sense for the insurance industry to be involved in these issues,” he said.
While these newer products of biotechnology may be distinct from GMOs, experts say that insurers are likely to take a similar approach, applying their experience with genetic engineering to gene editing and synbio.
“We have never excluded GMOs completely from our policies,” said Dr. Markus Kalin, head of global casualty risk engineering at XL Catlin, “and I think we would apply a similar approach to synthetic biology.”
Kalin pointed out that GMOs once posed a similar degree of unknown risk and fears of hidden dangers. Overwhelmingly though, “those fears have not been realized in this field.”
Taylor noted that the system of checks and balances in insurance allow it to undertake such risks in a controlled fashion, and the important part it will play as science advances.
“We, as responsible members of the risk management community, want to encourage a balance. We want to encourage innovation,” Gallagher’s Taylor said. &
2016’s Most Dangerous Emerging Risks
The Fractured Future Infrastructure in disrepair, power grids at risk, rampant misinformation and genetic tinkering — is our world coming apart at the seams?
Crumbling Infrastructure: Day of Reckoning Our health and economy are increasingly exposed to a long-documented but ignored risk.
Cyber Grid Attack: A Cascading Impact The aggregated impact of a cyber attack on the U.S. power grid causes huge economic losses and upheaval.
Fragmented Voice of Authority: Experts Can Speak but Who’s Listening? Myopic decision-making fostered by self-selected information sources results in societal and economic harm.
Four Loko Makers Denied Coverage
The makers of Four Loko alcoholic beverages were sued by families of individuals who died after ingesting the high-alcohol beverages in accidents or by acute alcohol poisoning.
Phusion, the manufacturer of the drinks, was insured by Selective Insurance Co. of South Carolina, whose policy had a liquor liability exclusion.
In 2013, Phusion filed a complaint against Selective in the Circuit Court of Cook County, Ill., saying the insurer had a duty to defend and indemnify it. Selective declined, citing the exclusion, and filed a motion to dismiss the complaint.
In its lawsuit, Phusion argued the underlying lawsuits were not excluded because the allegations “were not [solely] based on liquor liability, but were based on ‘stimulant liability.’ ” Four Loko beverages include caffeine, guarana and taurine, it said, arguing that the stimulants “operated to desensitize the consumers of Four Loko to the symptoms of intoxication and caused them to act recklessly.”
On Dec. 16, 2014, the circuit court granted Selective’s motion to dismiss. It ruled the “plain language of the liquor liability exclusion precluded coverage.”
That decision was upheld on Dec. 18, 2015, on appeal by Phusion to the 5th District Illinois Appellate Court. The appeals court agreed with a previous U.S. 7th Circuit Court of Appeals ruling in another case that held that Phusion’s arguments were an effort to “disguise the role that intoxication allegedly played in the underlying cases.”
Scorecard: Selective does not have to defend or indemnify Phusion.
Takeaway: For the insured to succeed, it would have had to prove that the allegations were “divorced from the serving of alcohol.”
Court: Hailstorm Damage Needs Proof
On June 21, 2011, vincent and peggy stagliano submitted a claim to the Cincinnati Insurance Co. and the Cincinnati Casualty Co. for damage from a May 24, 2011 hailstorm on one of 48 properties in Dallas that were insured.
That claim was paid, but claims later submitted by the pair claiming damage at other properties from the same hailstorm were denied. The Staglianos sued the insurers claiming breach of contract, among other allegations.
The insurance companies argued there was no evidence that the damage was caused by a hailstorm within the policy period. The insurers’ property claims manager stated the damage was from multiple storms, and could have occurred subsequent to policy expiration.
The district court concluded that the Staglianos’ expert witness, who said the damage occurred during the policy period, was not reliable. It dismissed the case.
The U.S. 5th Circuit Court of Appeals agreed on Dec. 11, 2015. Texas law, it said, requires clear proof that claimed losses occur within the policy period.
Scorecard: The insurance companies do not need to pay the claims.
Takeaway: The insured has the burden to offer proof that the claimed losses occurred during the policy period.
‘Hot Yoga’ Founder Gets Defense
In a lawsuit filed on June 13, 2013 in the U.S. District Court for the Central District of California, lawyer Minakshi Jafa-Bodden said she was forced to resign on March 1, 2013 to stop her investigations into a student’s rape allegation against Bikram Choudhury, the founder of “hot yoga.”
She also accused Choudhury of making offensive sexual gestures and leering at female staffers, among other allegations.
Choudhury sought defense and indemnification from Nationwide Insurance Company, which provided a directors and officers policy to USA Yoga, an organization run by Choudhury’s wife; and from Philadelphia Indemnity Insurance Co., which issued a commercial general liability policy to Choudhury and Bikram’s Yoga College of India.
Both insurers declined to provide defense or indemnification.
In a Dec. 9, 2015 ruling, the court decided that Philadelphia had a duty to defend. A day earlier, it ruled Nationwide did not.
The Philadelphia CGL policy covered personal and advertising injury that included “publication, in any manner, of material that slanders or libels a person or … disparages a person’s or organization’s goods, products or services.”
Jafa-Bodden’s allegations that Choudhury accused her of incompetence and engaged in improper and unethical sexual conduct fall within that coverage, the court ruled.
It ruled that an employment-related-practices exclusion did not apply because evidence indicated Jafa-Bodden was employed by the Indian law firm of Fox Mandal, which dispatched her to work for Choudhury, instructed him on her compensation, and continued to advise her on actions related to Choudhury’s legal affairs.
Since there was a dispute about her employment and thus, a potential for coverage, Philadelphia had a duty to defend, the court ruled.
Nationwide’s policy covered USA Yoga employees and volunteers for acts “in the discharge of their duties solely in [that] capacity.” The court ruled that Choudhury denied being an employee and other evidence concurred.
While Choudhury volunteered at competitions put on by USA Yoga, there is no evidence that Jafa-Bodden was ever at any of those events. In addition, his appearances were also on behalf of other organizations, so he was not acting “solely” as a volunteer for USA Yoga, and was not entitled to a defense from Nationwide.
Scorecard: Philadelphia Indemnity Insurance Co. must defend Bikram Choudhury in the lawsuit.
Takeaway: An insurer may rely on an exclusion to deny coverage only if it provides conclusive evidence that the exclusion applies.
To Better Control Total Workers Comp Costs, Manage Physical Medicine
Soaring drug prices get all the attention in the workers comp space. Meanwhile, another threat has flown under the radar.
More than 50 percent of lost time workers compensation claims involve physical medicine — an umbrella term encompassing physical therapy, occupational therapy, work conditioning, work hardening and functional capacity evaluation.
Spending on physical medicine accounts for 20 to 30 percent of total workers compensation medical costs, a percentage set only to increase in the coming years. Despite the rapid growth of this expense, very few employers are engaged in discussions around how best to manage it.
“Now is the time to take a look at physical medicine and think about how it impacts total cost of risk,” said Frank Radack, Vice President & Manager, Liberty Mutual Insurance, Commercial Insurance – Claims Managed Care. “Employers should investigate comprehensive solutions to keep costs manageable and to deliver quality, evidence-based care to injured employees.”
Liberty Mutual’s Frank Radack defines physical medicine and why it is so important in managing total workers compensation costs.
Upswings in both pure cost and utilization of physical medicine are driving the spending surge. State fee schedule changes are largely responsible for increases in cost. California, for example, has increased the cost of physical medicine services by 38 percent over the past two years, and will increase it a total of 64 percent by the end of 2017. North Carolina changed its approach to its fee schedule effective June 1, 2015, resulting in an almost 45 percent increase in the cost of the average physical therapy visit.
Increased utilization compounds rising prices. Low severity claims like soft tissue injuries typically involve physical therapy, especially when co-morbid conditions threaten to slow down recovery.
“When co-morbids are present, like obesity, more conditioning is necessary for recovery from injury,” Radack said. “With people staying in the workforce longer, we see these claims more often because these types of injuries and co-morbid conditions become more common as people age.”
De-emphasis on surgery also bolsters physical therapy prescribing as patients seek less invasive treatments that might enable a faster return to work, even in a light or transitional duty role. Sometimes, patients with a minor injury might seek out physical therapy on their own as a precaution after an injury or under the mistaken belief it will hasten recovery, even if evidence-based guidelines don’t call for it in every treatment plan.
“Now is the time to take a look at physical medicine and think about how it impacts total cost of risk. Employers should investigate comprehensive solutions to keep costs manageable and to deliver quality, evidence-based care to injured employees.”
–Frank Radack, Vice President & Manager, Liberty Mutual Insurance, Commercial Insurance – Claims Managed Care
“Without proper claims management procedures, some physicians might be inclined to prescribe physical therapy as a palliative measure, even when it doesn’t provide much benefit to the patient,” Radack said.
Brokers and buyers may not be able to do much about fee schedule changes, but they can partner with an insurer that better manages utilization through a multi-faceted claims system, qualified network vendors, data analytics, and peer interventions.
The keys to better managing the soaring cost of physical medicine.
“There is an opportunity to move physical medicine spending into network solutions and partnerships,” Radack said. A strong, collaborative network is key to maintaining direction over treatment decisions.
Liberty Mutual uses a proprietary data analytics program to study its providers’ prescribing and referral patterns and their outcomes. It then builds a network of point-of-entry general practitioners with a proven track record of optimal outcomes.
“The treating physician is a gatekeeper to other services, so it’s important to start there in terms of establishing a plan and making sure evidence based guidelines are followed,” Radack said.
Radack and his team use similar data analysis and partnerships to deploy networks pertaining only to physical medicine, so it can identify physical therapists who understand the occupational space and are focused on effective Return-to-Work (RTW). A provider who doesn’t understand RTW, or even know that the employer of an injured worker has a modified RTW program, may over-utilize PT. Getting employees with soft tissue injuries back into the work place is critical for delivering the best possible medical outcome and a timely recovery.
These therapists know the value of adjusting a treatment plan based on a patient’s progress, which often cuts unnecessary appointments and therapies.
“Our data analytics program is built internally by people who are aligned with the claims organization,” Radack said. “These insights drive our ability to shape networks and direct injured workers to providers with proven outcomes.”
Peer-to-peer interventions also play a big role in adjusting provider behavior and ensuring adherence to evidence-based guidelines. Liberty Mutual’s in house regional medical directors can bring their expertise to bear on challenging claims and discuss how to redirect treatment to meet these guidelines. Liberty Mutual also partners with experts to build networks of physical medicine and physical therapy providers who deliver quality outcomes cost-effectively and to asses a patient’s progress, working with providers to identify and resolve treatment issues.
Sharing information and measuring performance in these settings helps to change the environment around physical medical care. For example, interventions that steer physical therapists back to established, evidence-based medical treatment guidelines often reduce the use of passive therapy treatments, like hot and cold packs, which are not as effective and can slow down recovery.
“Active therapies that get people moving often help them get them back to work faster and at a lower cost,” Radack said. Utilization review also helps to identify unnecessary treatments and signals the insurer to communicate evidenced-based expectations with the therapist or prescribing physician.
Solutions in Action
Physical therapy offers great value in spite of rising prices — but only if it’s managed carefully.
An example of the benefits of managing physical medicine.
Take for example the case of a worker with a shoulder injury. In an unmanaged situation, a physical therapist may prescribe 12 appointments, and the injured worker will go through all 12 sessions with no pre-approval of the treatment plan and no interim checkup.
In a managed situation, the physical therapist may only prescribe eight sessions, because she understands the benefits of a faster return to work and sees that guidelines don’t dictate a full 12 sessions for this injury. Halfway through the eight sessions, she checks in on the patient’s progress and determines that only two more sessions are necessary given the recovery and the medical guidelines; and so adjusts the treatment plan to a total of six sessions.
In this scenario, managed care saves the cost of six sessions over the unmanaged situation, and the employee gets back to work faster with a healthy shoulder.
Ultimately, workers comp buyers can achieve cost savings by making treatment decisions that optimize patient outcomes, rather than cut pure cost. To achieve that, every player — point-of-entry physicians, physical therapists, medical directors, claims managers and patients — need to shoot for the common goal of shortening recovery time by following evidence-based medical guidelines.
“When medical experts and network vendors work in concert with each other, along with data analytics and research to back them up, we can drive down utilization while improving outcomes,” Radack said. “All of these working parts together are the solution to managing physical medicine costs.”
To learn more about Liberty Mutual’s Workers Compensation solutions, visit https://www.libertymutualgroup.com/business-insurance/business-insurance-coverages/workers-compensation
This article was produced by the R&I Brand Studio, a unit of the advertising department of Risk & Insurance, in collaboration with Liberty Mutual Insurance. The editorial staff of Risk & Insurance had no role in its preparation.