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De-Extinction Firm Unveils Progress Report on Thylacine Resurrection Initiative

# Stem Cell Editing, Comprehensive Genome Sequencing, and Cane Toad Mitigation: Groundbreaking Developments in De-Extinction and Conservation

In recent years, the idea of de-extinction—reviving species that have been absent from the planet for a long time—has intrigued both scientists and the general public. A key player in this arena is **Colossal**, a biotechnology company initially established to bring back the woolly mammoth. However, Colossal has broadened its focus to incorporate other extinct species such as the **dodo** and the **thylacine** (commonly referred to as the Tasmanian tiger). The company has made remarkable progress in stem cell editing, genome sequencing, and conservation initiatives aimed at safeguarding endangered species from extinction.

## The Thylacine: A Target for De-Extinction

The **thylacine**, a carnivorous marsupial endemic to Tasmania, became extinct in 1936 when the last known individual passed away in captivity. Although the biology of the thylacine is quite different from that of the woolly mammoth, Colossal’s advancements on this species have gained momentum thanks to the relatively short generation time of marsupials and their distinctive reproductive characteristics.

Marsupials, in contrast to placental mammals, give birth to underdeveloped offspring that continue to develop in the mother’s pouch. This unique aspect of their biology offers both challenges and opportunities for de-extinction endeavors. While the technology for altering marsupial reproduction is not as advanced as that available for placental mammals, recent progress in stem cell editing and genome sequencing is quickly bridging that gap.

## Cane Toad Mitigation: A Conservation Initiative

Alongside its de-extinction endeavors, Colossal has ventured into **conservation biology** with efforts to safeguard currently living species from extinction. A significant threat to Australian marsupials is the **cane toad**, an invasive species known for secreting **bufotoxins**, a category of toxic substances that can be deadly to native predators.

The bufotoxins attach to a protein known as **ATP1A1**, which manages ion transport across cell membranes. In the cane toad’s home range in Africa, various species have developed mutations in the ATP1A1 gene that diminish bufotoxin binding, rendering them immune to the toxin. Colossal’s research team, led by **Andrew Pask**, has successfully incorporated this mutation into a marsupial stem cell line’s genome, enhancing resistance to bufotoxins more than 6,000 times.

This advancement holds significant promise for **quolls**, a carnivorous marsupial species that faces endangerment due to cane toad consumption. Colossal’s team has produced quoll stem cell lines and is striving to introduce the cane toad resistance gene into the natural population. If achieved, this could avert the quoll from becoming another candidate for de-extinction.

## Genome Editing: Important Breakthroughs

One of the most pivotal components of de-extinction is **genome editing**. For the thylacine project, Colossal has performed over 300 distinct modifications to the genome of the **fat-tailed dunnart**, the thylacine’s closest living relative. These modifications aim to closely align the dunnart’s genome with that of the thylacine.

Additionally, the company has procured an almost complete genome sequence from a thylacine specimen preserved in ethanol for over a hundred years. This specimen contains both short DNA fragments and longer sequences exceeding 10,000 base pairs, facilitating a more thorough genome reconstruction. Presently, only 45 gaps remain in the thylacine genome, and the team anticipates resolving these shortly.

Such a level of genomic completeness is exceptional for an extinct species and instills a high degree of confidence that the team has uncovered all the significant genetic disparities between the thylacine and its closest living relatives.

## Messenger RNA: An Uncommon Discovery

In an extraordinary stroke of fortune, the thylacine specimen also yielded **messenger RNA (mRNA)** molecules, which are the products of active genes. This enables researchers to investigate which genes were functioning in specific tissues of the adult thylacine. For instance, mRNA analysis could shed light on the animal’s olfactory, gustatory, and visual capabilities, along with brain function.

This is a notable advancement since mRNA is generally quite delicate and seldom preserved in extinct species. By analyzing these molecules, scientists can acquire a deeper understanding of the thylacine’s biology, which could prove essential for accurately recreating the species.

## Thylacine Wolf Accelerated Regions (TWARs)

One particularly fascinating element of Colossal’s research is the identification of **Thylacine Wolf Accelerated Regions (TWARs)**—DNA segments that appear to have undergone rapid evolution in both thylacines and wolves. Despite being

Increasing Streaming Subscription Prices Alongside Diminishing Content Quality

### Decrease in Viewer Satisfaction with Streaming Media: An Escalating Issue for the Sector

Subscription rates for video streaming services have been consistently rising, yet surveys indicate that viewers are increasingly dissatisfied with the content on offer. As the streaming sector endures mounting financial challenges, the “Peak TV” era appears to be diminishing, prompting subscribers to reevaluate the worth of their subscriptions.

#### The Conclusion of Peak TV

As 2024 commenced, the industry started to announce the conclusion of “Peak TV,” a concept introduced by FX Networks chairman John Landgraf. This phase, which lasted over ten years, was characterized by a surge in high-quality, original programming that drew millions to streaming services. Series like *The Wire*, *Breaking Bad*, and *Game of Thrones* epitomized this illustrious period in television, during which streaming platforms vied intensely to create critically cherished content.

However, as streaming companies grapple with achieving or sustaining profitability, 2024 witnessed a decrease in the volume of new scripted series for the first time in over a decade, according to FX Research. This reduction in original content has mirrored a discernible decline in viewer satisfaction.

#### Diminishing Subscriber Satisfaction

Recent polling data reveals that overall content satisfaction among streaming service users has been on a downward trend for the past few years. While the decrease in perceived quality remains relatively slight, it is still alarming, particularly in light of the regular hikes in subscription fees.

For instance, the most viewed TV series in 2023 was *Suits*, a show that first aired on the USA Network and concluded in 2019. The fact that an older, non-original program led the streaming ratings underscores the industry’s difficulties in delivering new, engaging content that captivates viewers.

#### Survey Results: A Distinct Decline

Earlier this year, TiVo published its *Q2 2024 TiVo Video Trends Report: North America*, based on a survey of 4,490 individuals in the US and Canada. The findings displayed a drop in the percentage of subscribers who rated the quality of content from their subscription video-on-demand (SVOD) services as “moderate to very good.” This trend was evident in both ad-supported and ad-free streaming services.

In Q2 2022, 78.6% of participants rated their ad-free SVOD service as having “moderate to very good” content. By Q2 2024, this figure had decreased to 74.5%. For ad-supported services, the fall was even more pronounced, dropping from 74.2% in Q2 2023 to merely 60.8% in Q2 2024.

#### Financial Difficulties and Content Quality

Scott Maddux, VP of global content strategy at TiVo’s parent company Xperi, highlighted several potential factors contributing to the decline in satisfaction. One reason is the transition towards ad-supported models, which may foster the impression of diminished content quality. Furthermore, many streaming firms are encountering financial obstacles, which could hinder their capacity to create new, high-caliber content.

“As an increasing number of consumers migrate to ad-supported SVOD services, the perception of content quality could also have shifted downward somewhat,” Maddux articulated. He also pointed out that the overall volume of new original content on SVODs might have declined year-over-year, as various streamers continuously strive to meet profitability goals.

#### Effects of Strikes and Budget Reductions

The downturn in content quality is not solely attributed to financial hurdles. The sector has also faced external influences, such as the writers’ and actors’ strikes in Hollywood in 2023. These labor disputes disrupted production timelines and postponed the release of several eagerly awaited shows and films.

Streaming companies have likewise executed substantial budget reductions in recent years. As reported by *Variety*, firms like Amazon, Disney, Netflix, and Warner Bros. Discovery are anticipated to decrease their content expenditures from 2023 to 2026 in comparison to the preceding five years. While worldwide content investment is still projected to rise, much of this increase will stem from climbing production costs rather than enhanced content volume or quality.

#### Subscriber Expectations and the Future of Streaming

As streaming services continue to elevate pricing, subscribers are looking for greater value. TiVo’s survey identified content quality as one of the leading factors prompting individuals to sign up for a new streaming platform. The primary motivations for subscribing include a vast library of quality programming, specific shows or films, and compelling original content.

Yet, the era of streaming services providing an unceasing flow of must-see content may be coming to a close. A report from *Bloomberg* noted that Netflix, for instance, is shifting its strategy towards creating fewer, higher-quality films instead of acquiring content from film studios. This change signifies a broader industry trend where streaming providers are becoming more selective regarding the projects they support.

#### The Urgency to Enhance

With the competition in the streaming arena intensifying, the pressure on providers to improve their offerings continues to grow.

Lawsuit Claims Pharma Firm Employed Code Terms to Promote Fake Weight-Loss Medication

## Pivotal Peptides Charged with Distributing DIY Tirzepatide Kits Following Cease-and-Desist Notice

In a strange and alarming turn of events, a drug supplier based in Washington, Pivotal Peptides, has been accused of marketing do-it-yourself (DIY) kits for crafting counterfeit versions of prescription-only medications for diabetes and weight management, such as Zepbound and Mounjaro. These medications, which feature the active substance tirzepatide, are generally utilized to manage type 2 diabetes and are increasingly sought after for their weight-loss properties. Nonetheless, Pivotal Peptides purportedly evaded legal and safety protocols by presenting customers with the means to prepare their own injectable copies of these drugs without needing a prescription or a medical evaluation.

### The Reported Scheme

A lawsuit initiated by pharmaceutical behemoth Eli Lilly, the producer of tirzepatide-based drugs Zepbound and Mounjaro, alleges that Pivotal Peptides sold DIY kits containing a white powder that customers were directed to combine with sterile water to produce an injectable solution. The powder was labeled as a “research chemical for lab research and veterinary use only,” raising significant alarms regarding its safety and suitability for human consumption.

The kits included explicit instructions, urging customers to sanitize their home work area and utilize a 30-gauge syringe for administering the self-made concoction. This method starkly contrasts with the controlled and sterile conditions under which pharmaceutical-grade drugs are formulated, evaluated, and dispensed. The absence of regulatory oversight and the hazards of contamination or incorrect dosing present serious health threats to consumers.

### Eli Lilly’s Legal Proceedings

In July, Eli Lilly issued a cease-and-desist letter to Pivotal Peptides, cautioning the firm that it was vending a research-grade variant of tirzepatide that had not undergone purification to pharmaceutical standards and lacked approval for human usage. Despite this warning, Pivotal Peptides allegedly persisted in its activities, even altering its website to claim it was “down for maintenance” while instructing clients to place orders via email.

In a notably brazen action, Pivotal Peptides’ registered agent, Elizabeth Gately, allegedly dispatched an email to clients advising them to use coded terminology when ordering tirzepatide. In the email, the product was referenced as “11 mg” instead of its official name, likely as an attempt to avoid additional legal scrutiny. Gately identified the product as Pivotal Peptides’ top seller and motivated customers to continue ordering it under the altered code name.

### Safety Concerns and Legal Consequences

Eli Lilly’s lawsuit targeting Pivotal Peptides forms a segment of a wider legal struggle regarding the illicit sale of counterfeit versions of tirzepatide. The pharmaceutical entity has lodged various lawsuits against suppliers of unapproved iterations of its medications, citing alarming threats to patient safety. In its statement, Lilly underscored that these untested, non-pharmaceutical-grade products could be hazardous, particularly since they are marketed without prescriptions or medical supervision.

The Food and Drug Administration (FDA) has also expressed apprehensions about the safety of compounded variations of GLP-1 medications like tirzepatide, which are sometimes fabricated by licensed pharmacies during drug shortages. Nonetheless, the FDA has cautioned that these compounded forms may not fulfill the same safety and efficacy regulations as the original, FDA-sanctioned drugs. In fact, the FDA has issued several warnings concerning the potential risks of utilizing unapproved GLP-1 medications for weight reduction.

### The Wider Legal Framework

The legal environment regarding tirzepatide and other GLP-1 medications is intricate. Compounding pharmacies may create off-brand versions of these drugs when shortages occur, but this practice has come under investigation. In early October 2024, the FDA declared that the tirzepatide shortage had ended, which would have curtailed the capability of compounding pharmacies to persist in producing these medications. However, after encountering lawsuits from compounding pharmacies, the FDA resolved to reassess its ruling, further complicating the matter.

Eli Lilly’s lawsuits, including the action against Pivotal Peptides, spotlight the escalating friction between pharmaceutical corporations, compounding pharmacies, and unlicensed vendors. While compounding pharmacies function within a legal framework, entities like Pivotal Peptides seem to be capitalizing on loopholes and distributing potentially harmful products to consumers.

### Conclusion

The action against Pivotal Peptides highlights the critical need for regulatory supervision within the pharmaceutical sector. Distributing DIY kits for crafting injectable medications without appropriate testing, endorsement, or medical oversight is not only unlawful but also presents substantial dangers to public health. As the legal conflicts surrounding tirzepatide and other GLP-1 medications persist, it is imperative for consumers to remain conscious of the hazards linked to unapproved and untested pharmaceuticals.

Pharmaceutical firms like Eli Lilly, in conjunction with regulatory agencies such as the FDA, are striving to guarantee that only safe, vetted, and sanctioned drugs are accessible to the public. Meanwhile, consumers must exercise caution.