Wednesday, April 17, 2024

Bio-Economy Thanatopolitics: Gene-Therapy Risks - Past, Present, and Future

In 2007, Rick Weiss reported for the Washington Post potential hazards of genetic medicine and the failed regulatory apparatuses designed to protect patient safety and public health.

You will find below a short excerpt from the article, which is indexed online by Georgetown, but no longer seems to be available. Here is the link to the Georgetown index:

The content of the original article appears to have been taken down by Google in response to a recent (2024) DMCA (Copyright) Complaint:

I will not be posting the entire article and the purpose of the excerpted materials is educational:

Weiss, R. (2007, August 6). Death points to risks in research. The Washington Post, A1.

Robb Mohr sat by his wife's hospital bed two weeks ago, trying to take it all in. His wife, Jolee Mohr, was breathing with the help of a ventilator in a Chicago intensive care unit -- her body bloated from internal bleeding, her liver failing -- and no one could figure out what was wrong with her.

Robb Mohr had his suspicions. Jolee, 36, had been feeling fine just a few weeks earlier, save for occasional stiffness from her arthritis. Her decline had begun the day after her right knee was injected with an experimental drug made of genetically engineered viruses. Doctors at the hospital shared his concern.

Jolee Mohr died from massive bleeding and organ failure July 24, leaving behind a 5-year-old daughter and a host of questions about why she was recruited into a gene therapy experiment whose chief goal was to test the safety of a novel arthritis treatment that had virtually no chance of helping her.

No one knows yet whether the treatment was to blame. Of the dozens of other volunteers who got the injections, only Mohr suffered anything more than short-lived side effects, said officials at Targeted Genetics Corp., the Seattle company that makes the product. The Food and Drug Administration and the company are investigating.

But a close look at the events leading to Mohr's death reveals failures in the safety net that is supposed to protect people from the risks of medical experimentation -- and in particular, the risks of gene therapy, which for 17 years has struggled in vain to live up to its optimistic name.

Breaches of clinical research standards and a federal oversight system that allowed key decisions to be made behind closed doors may have helped draw Mohr into an experiment that was not, her husband says, what she thought it was....

... Suspecting a possible link to the experimental drug, the doctors in Chicago contacted the FDA.

Federal regulations require a company to report any serious complications that are even "possibly" related to an experimental treatment "as soon as possible" and no later than seven days after learning of it. But Targeted Genetics and Trapp had at first classified the problems as not serious, and later classified them as serious but unrelated to the treatment. So no FDA report was made, and the study went on, with other volunteers unaware of the problems.

That reflects a widespread problem in clinical trials, said Adil Shamoo, a professor at the University of Maryland School of Medicine and editor in chief of the journal Accountability in Research.

"There are no uniform standards for 'adverse events' reporting," Shamoo said. "And there is no motivation to report them. . . . No one wants to show their dirty linen." Dirty linen can drag down a company's bottom line, and Targeted Genetics, like all companies, puts a lot of work into keeping that line afloat.

One reassuring aspect of tgAAC94's engineering is that genes required for replication have been removed, so the viruses cannot make more of themselves. But animal studies conducted by the company have shown that the product can escape from the joint space and travel about the body, perhaps catching the attention of the immune system. In general, the immune system mounts much more robust -- sometimes dangerously robust -- responses after a second exposure. In fact, both shots Mohr got were the real thing, the company said.

In order to learn more about Targeted Genetics, I tracked the company over time. The company assumed the name of AmpliPhi Biosciences Corporation in March 2011. The chain of acquisitions after then has been non-stop. 

The life-sciences and bio-engineering were supposed to fuel the 21st century's economic engine, as optimistically reported in 2011:

“...the entire complex of the life sciences and the biopharmaceutical industry has been portrayed as the industry that will dominate the economic regime of accumulation in the new century” p. 43

Styhre, A., & Sundgren, M. (2011). The Bioeconomy, Biocapital and the New Regime of Science-based Innovation. In Venturing into the Bioeconomy: Professions, Innovation, Identity (pp. 42-99). London: Palgrave Macmillan UK. P. 43

In 2012, the Biden administration issued an executive order on this "bio-economy," pushing to make it a reality despite years of failed projects and lack of successes due to the complexities of biological systems and the challenges of delivering genetic changes using (primarily adeno) viruses. 

The lipid nanonparticles that encase the experimental mRNA vaccines were supposed to be less risky than the viral vectors but have turned out to be highly inflammatory, persistent and disease-producing. The lipid nanoparticles may also produce clots.

Robert Malone was involved in early testing of these lipid nanoparticles and his explanations for their failures are highly instructive. You can read his work here:

Review and Commentary: "Strategies to reduce the risks of mRNA drug and vaccine toxicity"

Malone, R.W. (2023, Nov 16). Statement and Testimony, COVID-19 Vax Injuries. A statement prepared for the November 13 House of Representatives Hearing.

Documentation of the risks of lipid nanoparticles can be found elsewhere, as well:

Lipid nanoparticle structural components, production methods, route of administration and proteins produced from complexed mRNAs all present toxicity concerns.”

Bitounis, D. et al. Strategies to reduce the risks of mRNA drug and vaccine toxicity. Nat Rev Drug Discov. 23 January 2024.; PMID: 38263456

Biden's bio-economy is challenged by the complexity of human biology and by the challenges associated with creating safe delivery mechanisms for genetic engineering.

Even CRISPR, that much heralded tool of genetic engineering, has been flawed with unexpected downstream mutation effects from gene editing:

Schaofer, K.A., Wu, W-H., Colgan, D.F., Tsang, S.H., Bassuk, A.G., & Mahajan, V. B. (2017) Unexpected mutations after CRISPR-Cas9 editing in vivo. Nature Methods, 14(6), 547.

To the Editor: CRISPR–Cas9 editing shows promise for correcting disease-causing mutations. For example, in a recent study we used CRISPR-Cas9 for sight restoration in blind rd1 mice by correcting a mutation in the Pde6b gene1. 

However, concerns persist regarding secondary mutations in regions not targeted by the single guide RNA (sgRNA)2. Algorithms generate likely off-target sites for a given gRNA, but these algorithms may miss mutations.

Whole-genome sequencing (WGS) has been used to assess the presence of small insertions and deletions (indels)3 but not to probe for single-nucleotide variants (SNVs) in a whole organism. We performed WGS on a CRISPR–Cas9-edited mouse to identify all off-target mutations and found an unexpectedly high number of SNVs compared with the widely accepted assumption that CRISPR causes mostly indels at regions homologous to the sgRNA.

Downstream mutations! Yikes. Turns out that the mRNA vaccines produced mutation errors as well!

Joe Pinkstone, Science Correspondent 6 December 2023 One in four who had Pfizer Covid jabs experienced unintended immune response

The upshot of all this is that our institutional authorities and decision-makers are going to move ahead with the bioeconomy whether it is ready or not for the safety engineering the "meat" that is our bodies and minds:

Executive Order on Advancing Biotechnology and Biomanufacturing Innovation for a Sustainable, Safe, and Secure American Bioeconomy. September 9, 2022.

Section 1. Policy. It is the policy of my Administration to coordinate a whole-of-government approach to advance biotechnology and biomanufacturing towards innovative solutions in health, climate change, energy, food security, agriculture, supply chain resilience, and national and economic security. Central to this policy and its outcomes are principles of equity, ethics, safety, and security that enable access to technologies, processes, and products in a manner that benefits all Americans and the global community and that maintains United States technological leadership and economic competitiveness.

Biotechnology harnesses the power of biology to create new services and products, which provide opportunities to grow the United States economy and workforce and improve the quality of our lives and the environment. The economic activity derived from biotechnology and biomanufacturing is referred to as “the bioeconomy.” 

The COVID-19 pandemic has demonstrated the vital role of biotechnology and biomanufacturing in developing and producing life-saving diagnostics, therapeutics, and vaccines that protect Americans and the world. Although the power of these technologies is most vivid at the moment in the context of human health, biotechnology and biomanufacturing can also be used to achieve our climate and energy goals, improve food security and sustainability, secure our supply chains, and grow the economy across all of America.

For biotechnology and biomanufacturing to help us achieve our societal goals, the United States needs to invest in foundational scientific capabilities. 

We need to develop genetic engineering technologies and techniques to be able to write circuitry for cells and predictably program biology in the same way in which we write software and program computers; unlock the power of biological data, including through computing tools and artificial intelligence; and advance the science of scale‑up production while reducing the obstacles for commercialization so that innovative technologies and products can reach markets faster.

Simultaneously, we must take concrete steps to reduce biological risks associated with advances in biotechnology. We need to invest in and promote biosafety and biosecurity to ensure that biotechnology is developed and deployed in ways that align with United States principles and values and international best practices, and not in ways that lead to accidental or deliberate harm to people, animals, or the environment. 

In addition, we must safeguard the United States bioeconomy, as foreign adversaries and strategic competitors alike use legal and illegal means to acquire United States technologies and data, including biological data, and proprietary or precompetitive information, which threatens United States economic competitiveness and national security.

cont. at link above




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