How to Create a Genetic Condition
Alpha-1 Antitrypsin Deficiency and the Architecture of Circular Evidence
How to Explain This to a 6-Year-Old
Some people say there’s a broken part inside you that might make you sick. They say they know it’s broken because of special tests. But when you ask how they know the tests are right, they point to studies. When you ask how the studies know, they point to other studies. When you ask how those studies know, they point back to the first ones.
Nobody actually checked if the broken part makes you sick. They just kept pointing at each other until everyone believed it.
Meanwhile, the people who say you’re broken sell the medicine for broken people. They make a lot of money. They have a big building and a phone number you can call. They seem very sure.
But the pointing-at-each-other isn’t proof. It’s a circle.
1. The Infrastructure
The Alpha-1 Foundation holds $44 million in assets. It employs staff across research, patient education, and advocacy programs. It funds a national registry, sponsors clinical studies, operates a detection program, and maintains collaborative agreements with fifteen pharmaceutical companies through a for-profit subsidiary called The Alpha-1 Project. In fiscal year 2024, it disbursed $3.2 million in research grants and received $2 million from AlphaNet, a related organization.
The Foundation operates a genetic counseling hotline: 1-855-476-1227. Patients can call to discuss the implications of their diagnosis, plan their families, and understand their genetic risk.
Visit the Foundation’s website and you will find confident clinical claims. “People who inherit two ZZ mutations—one from each parent—have extremely low levels of AAT in the blood, which increases their risk of developing lung disease.” The condition “can cause damage to the lungs and/or the liver.” It is “progressive, which means it may worsen over time.” There are approximately 100,000 Americans living with the condition, the website states, and 19 million carriers. The guidance is clear: get tested, know your status, call the hotline.
“Because Alpha-1 is inherited,” the website explains, “there is no way to prevent it.”
What evidence supports these claims? The Foundation cites peer-reviewed research. Clinical guidelines. Mouse studies. Population genetics. The literature appears substantial. Trace the citations, however, and a different picture emerges—one in which confident claims rest on studies that assume what they purport to prove, cite each other in closed loops, and contain admissions that contradict the public-facing message.
This is how a genetic condition is created.
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2. The Clinical Guidance
The Foundation’s flagship claim—that ZZ mutations cause low AAT protein levels, which increase lung disease risk—traces to clinical guidance documents like GeneReviews, a widely referenced summary hosted by the National Institutes of Health. GeneReviews states that alpha-1 antitrypsin deficiency “can present with hepatic dysfunction in individuals from infancy to adulthood and with chronic obstructive pulmonary disease (emphysema, chronic bronchitis, and/or bronchiectasis), characteristically in individuals older than age 30 years.”
This sounds definitive. But read further and qualifications appear. “Phenotypic expression varies within and between families.” Nonsmokers “may have a normal life span, but can also develop lung and/or liver disease.” The document notes that only 5,000 to 10,000 individuals in the United States have been identified with the condition—despite prevalence estimates suggesting it should be far more common.
What evidence does GeneReviews cite for the claim that the gene causes disease?
It cites mouse studies.
3. The Mouse Model
In 2018, researchers at the University of Massachusetts Medical School published a paper in the Proceedings of the National Academy of Sciences titled “Editing out five Serpina1 paralogs to create a mouse model of genetic emphysema.” Using CRISPR technology, they knocked out all five copies of the Serpina1 gene in mice—necessary because mice have five copies where humans have one, an immediate signal that the biology differs.
The paper announces its significance directly: “This mouse model spontaneously develops lung disease and recapitulates many aspects of the human disease.”
What do the mice actually show?
The researchers report that the knockout mice have “normal behavior, lifespan, and gender distribution.” They develop emphysema only at advanced age—after 35 weeks, with clear symptoms at 50 weeks. In younger mice, emphysema could be induced by exposing them to lipopolysaccharide, a bacterial toxin.
The mice are healthy. They live normal lives. They develop lung changes late in life, or when exposed to environmental insults.
Examine the specifics. The researchers measured pulmonary mechanics at 35 and 50 weeks of age. At 35 weeks, they found “early signs” of emphysema. At 50 weeks—roughly equivalent to middle age in human terms—the mice showed increased lung compliance, a marker of emphysematous change. But the paper’s own “Significance” box announces that the mice “spontaneously develop lung disease and recapitulates many aspects of the human disease” while the results section shows animals living their full lives and developing changes only in advanced age.
The researchers also induced emphysema in younger mice using a “two-hit” lipopolysaccharide challenge—essentially, bacterial toxin. Wild-type mice recovered from this challenge. The knockout mice did not. This demonstrates that without the AAT protein, mice are more vulnerable to environmental insult. It does not demonstrate that the gene itself causes disease. It demonstrates that removing a protein reduces resilience to external damage.
The paper acknowledges a fundamental problem buried in the methodology: mice have five Serpina1 genes, humans have one. The authors note that earlier attempts to knock out individual mouse genes proved embryonically lethal, which they find puzzling since “SERPINA1 null humans are viable.” The systems are not equivalent.
What evidence does this paper cite for believing the gene causes human disease?
It cites clinical observations.
The circularity is built into the research design. Researchers justified creating the mouse model because clinical observations suggested the gene was important. The mouse model is then cited as evidence that the gene causes disease. But the model was created on the assumption that it would—the conclusion preceded the experiment.
4. The Follow-Up
A 2022 follow-up study examined the liver transcriptome of these same knockout mice. The researchers found changes in inflammatory and metabolic pathways. They suggest these findings have implications for human therapy development.
Then they state directly: “The differences between the Serpina gene system in mice and humans create a limitation of these model-based studies.”
The mouse model doesn’t match human biology. The researchers say so themselves.
What do they recommend?
“Further CRISPR-knock out or gene silencing of SERPINA1 in human-derived organoid models would be warranted.”
The gold-standard animal model, cited by clinical guidelines as evidence that the gene causes disease, doesn’t demonstrate causation. The mice are healthy. The biology doesn’t translate. The researchers themselves call for different models. Yet this paper is cited as foundational evidence.
What evidence does this paper cite for the broader claim of genetic causation?
It cites the clinical literature—the same literature that cites the mouse studies.
5. The Population Studies
Population genetics studies add another layer. A 2021 review cataloging SERPINA1 variants acknowledges that over 500 have been identified, with researchers “only aware of the tip of the iceberg.” The clinical significance of most variants remains unknown. The review notes that some researchers have “already questioned” whether the standard protective threshold applies universally, given that patients above the threshold still develop symptoms while many below it remain healthy.
The variants are cataloged. Frequencies are calculated. Associations are noted. The question of whether any variant actually causes disease—rather than correlating with it—goes unaddressed.
What evidence do population studies cite for genetic causation?
They cite clinical observations and mouse models.
6. The Testing Problem
Testing methodology papers reveal additional problems. A 2021 review in Therapeutic Advances in Chronic Disease states plainly: “Due to the diversity and novelty of rare variants, the clinical significance of many is largely unknown. There is, therefore, a lack of guidance on how patients should be monitored and treated when the clinical significance of their variant combination is unclear or variable.”
Over 200 variants have been documented. For most, no one knows what they mean clinically. The review describes the limitations of standard testing: isoelectric focusing cannot identify certain heterozygous variants, targeted PCR panels cannot detect novel mutations, and patients receiving augmentation therapy will be misidentified by phenotyping methods.
The technical details matter. Isoelectric focusing—the traditional testing method—separates proteins based on their electrical charge. Different AAT variants migrate to different positions, creating a pattern that can be read. But the method requires expert interpretation, cannot detect all variant combinations, and fails entirely for patients already receiving AAT therapy, since the infused protein masks the patient’s own production.
Targeted PCR testing offers rapid identification of common variants like Z and S, but cannot detect novel mutations. Given that researchers acknowledge being aware of only “the tip of the iceberg” of existing variants, a testing methodology that cannot identify novel variants will necessarily miss cases while potentially misclassifying others.
A 2012 case report describes a patient with low circulating AAT who was misdiagnosed by standard isoelectric focusing—the conventional testing method—as having a Z/M2 phenotype. Genetic sequencing revealed an entirely different, novel mutation. The patient had no symptoms despite deficiency-level protein.
An asymptomatic patient. Misdiagnosed by standard testing. Carrying a variant of unknown clinical significance.
This is the testing infrastructure on which diagnoses depend.
What evidence do these papers cite for the underlying genetic causation?
They cite clinical guidelines, mouse models, and population studies.
7. The Therapy Research
Therapeutic research completes the circle. A 2018 paper developing mRNA therapy for alpha-1 antitrypsin deficiency tested the treatment in wild-type mice—not even a disease model—and demonstrated that the mRNA reached liver and lung tissue. The paper assumes throughout that the gene causes disease and that replacing the protein will help.
The final line acknowledges: “Further research needs to be conducted in an AATD disease model.”
The therapy was developed and tested without demonstrating it addresses actual disease. The assumption of genetic causation preceded the research; the research did not establish it.
What evidence does this paper cite for the need it addresses?
Clinical observations. Mouse models. Population studies.
8. The Loop
The citation structure forms a closed loop.
The Foundation claims ZZ mutations increase lung disease risk. What evidence supports this? Clinical guidelines like GeneReviews. What evidence does GeneReviews cite? Mouse studies showing emphysema in knockout animals. What justifies believing the mouse model translates to humans? Clinical observations of patients with low AAT who develop lung disease. What establishes that low AAT causes the lung disease, rather than correlating with it? The assumption that the gene is causative—the same assumption the mouse model was supposed to prove.
Mouse models cite clinical observations as justification for their experiments. Clinical guidelines cite mouse models as mechanistic evidence. Population studies cite both to establish prevalence and risk. Therapeutic research cites all three to justify intervention. Each paper assumes genetic causation based on the others. None independently demonstrates that a DNA variant initiates disease.
9. The Penetrance Problem
The GeneReviews document, the authoritative clinical summary, acknowledges the gaps while maintaining diagnostic confidence. It reports that only 10 to 15 percent of adults with severe deficiency develop significant liver disease. The remaining 85 to 90 percent carry the same “disease-causing” variant and do not develop the condition.
If the gene caused the disease, this would be impossible.
Consider the arithmetic. The Foundation claims 100,000 Americans have alpha-1 antitrypsin deficiency. If 85-90 percent of those with severe deficiency never develop significant liver disease, then 85,000-90,000 people carry the variant without the consequence it supposedly causes. The clinical literature calls these people “affected” while acknowledging they will never be affected.
The official explanation invokes environmental factors—smoking, exposures, lifestyle—to explain why most carriers remain healthy. Genetics has a term for this: incomplete penetrance. But consider what this admission means. If environment determines whether a “disease-causing” variant actually causes disease, then environment is the operative variable, not the gene. The variant becomes a bystander, present but not determinative. The diagnosis points at the gene while conceding that something else controls the outcome.
The same pattern appears with lung disease. Studies following newborns with severe AAT deficiency through age 32 found that most non-smoking adults showed no physiologic or CT evidence of emphysema. People with the variant—the same variant that supposedly causes disease—remained healthy for three decades. The GeneReviews document acknowledges this directly, noting that longer-term follow-up studies are not currently available.
The Foundation’s website states it plainly: “Many people with Alpha-1, including those with SZ or ZZ mutations, have no symptoms of the condition.”
This sentence appears on the same page that describes Alpha-1 as a serious progressive disease requiring medical attention. Both claims are presented as compatible. They are not.
The distinction matters. A gene that causes disease is a cause. A gene that correlates with disease in some people under some circumstances is a risk correlate. By naming alpha-1 antitrypsin deficiency a “genetic condition” rather than a “genetic predisposition,” the Foundation performs a linguistic sleight of hand. The framing implies determinism while the data shows correlation. Patients receive a diagnosis that sounds like a verdict when it is, at most, a probability—and a low one.
Consider a falsification question: if the SERPINA1 gene were edited out of the human genome tomorrow, but smoking, air pollution, alcohol use, and occupational exposures remained unchanged, what proportion of lung and liver disease would disappear?
If the honest answer is “very little,” the diagnosis has been miscast. The gene is not the cause. It is a marker that correlates with vulnerability in people already being damaged by something else.
10. The Admissions
The research papers contain their own contradictions, visible to anyone who reads past the abstracts.
Foundation Claim Literature Admission ZZ mutations cause lung disease “Nonsmokers may have a normal life span” Mouse models prove causation “Normal lifespan”; “differences between Serpina gene system in mice and humans create a limitation” Testing identifies disease “Clinical significance of many variants is largely unknown” 100,000 Americans are affected 85-90% of those with severe deficiency never develop significant liver disease
The 2018 mouse study: “This mouse model has a normal lifespan but presents with a respiratory phenotype that recapitulates many aspects of the human disease.” Normal lifespan. Healthy mice. Yet cited as proof of disease causation.
The 2022 follow-up: “The differences between the Serpina gene system in mice and humans create a limitation of these model-based studies.” The model doesn’t translate. Yet it remains the foundational evidence.
The 2021 testing review: “The clinical significance of many [variants] is largely unknown.” Most diagnoses rest on variants no one understands. Yet testing is recommended and performed.
The GeneReviews summary: “Nonsmokers may have a normal life span.” The gene doesn’t determine the outcome. Yet the diagnosis is presented as meaningful.
These admissions appear in the same documents cited as proof that genetic diagnosis is reliable. The researchers know the limitations. They publish them. The limitations do not alter the diagnostic confidence or the clinical recommendations that flow from it.
11. The Money
The Alpha-1 Foundation’s financial statements reveal the infrastructure this circular evidence supports.
Total assets: $44 million, including $29.7 million in current investments and $11.3 million in non-current investments. Annual program expenses: $8.6 million. Research and clinical studies expenditure: $5.6 million. Patient education: $2.6 million. The Foundation receives $2 million annually from AlphaNet, a related organization that provides facility space and operational support.
The detailed expense breakdown shows where the money flows: $3.2 million in research grants, $1.8 million in salaries for research and clinical staff, $1.4 million for conferences and meetings, $1.6 million in contract services. The infrastructure employs people, funds institutions, and maintains its own momentum.
The Alpha-1 Project, a for-profit subsidiary incorporated in Delaware in 2009, has contributed approximately $3.9 million to fifteen pharmaceutical companies “as part of a strategy to accelerate finding cures and treatments for the Alpha-1 disorder.” Each contract provides that “if the research is successful, TAP would receive royalties and milestone payments based on the success.” If research is abandoned, TAP receives rights to the licenses and research results.
The subsidiary’s explicit mission: “providing critical funding to expedite the commercialization of therapies.”
The Foundation’s mission includes “the commercialization of therapies for the elimination of COPD and liver disease caused by Alpha-1.” The language assumes causation. The research is organized around that assumption. The funding flows to support it.
Augmentation therapy—weekly or biweekly intravenous infusions of alpha-1 antitrypsin protein—represents the current standard of care. Patients diagnosed with the condition are offered lifetime treatment. The infrastructure exists to identify them, counsel them, treat them, and monitor them. The research justifying this infrastructure cites itself.
12. The Method
What would it take to demonstrate that a genetic variant causes disease?
Scientific causation requires showing that A produces B—not merely that A and B appear together. Resistance to antibiotics correlates with hospital stays, but hospitals do not cause resistance. A rooster crows before dawn, but the rooster does not cause the sunrise. Correlation requires additional evidence before it can support causation.
A gene that causes disease should produce disease in most carriers, without requiring environmental factors to activate it. A gene that requires smoking, pollution, or alcohol to manifest is not a cause—it is a bystander present at the scene.
How is genetic causation established in practice?
A condition exists. Researchers compare DNA from affected individuals to DNA from unaffected individuals. A variant appears more frequently in the affected group. The variant is assigned to a database coordinate labeled a “gene.” The condition is declared genetic.
Notice what is missing. No experiment demonstrates the variant initiating the disease in isolation. No one observes the mechanism by which a DNA sequence produces illness inside a living body. Identification follows outcome; causation is inferred after the fact, not demonstrated beforehand.
The methodology would not meet engineering standards for causal verification. Observation of correlation, followed by assertion of causation, followed by the naming of the correlation as proof—this is circular reasoning dressed in technical language.
In the case of alpha-1 antitrypsin deficiency, the circle is explicit. The mouse model is justified by clinical observations. Clinical guidance is justified by the mouse model. Population studies cite both. Therapy development cites all three. Each link in the chain assumes what the previous link was supposed to prove.
13. The Pattern
The pattern extends beyond this single condition.
Good Morning Britain recently ran a segment urging Black people to get tested for the APOL1 gene, which supposedly puts 1 in 10 people of Caribbean or African heritage at risk for kidney failure. The framework is identical: a population is told it carries genetic material requiring medical surveillance. That Black communities face disproportionate environmental burdens—toxic exposures, food deserts, medical neglect, chronic stress—disappears from the analysis. The problem is relocated from environment to genome.
The methodology is portable. Find a condition. Compare DNA. Identify a correlating variant. Declare genetic causation. Build an infrastructure of testing, counseling, and treatment. Fund research that assumes the conclusion. Cite that research as evidence. The loop closes.
Dr. Toby Rogers, a political economist whose testimony before the U.S. Senate introduced concepts that should have reshaped public understanding of medicine, named this process: epistemic capture. It occurs when an industry controls the conditions of knowledge production itself—what gets researched, how it is studied, what counts as evidence, what gets published. When you capture regulation, you influence decisions. When you capture epistemology, you control reality itself.
The pharmaceutical industry has achieved unprecedented colonization of medical knowledge production. Medical school curricula, clinical guidelines, journal articles, regulatory agencies—each element reinforces the others. Doctors recommend genetic testing not from malice but from training. They dismiss patient questions not from cruelty but from epistemic limitation. They cannot see what their education did not prepare them to recognize.
The streetlight effect compounds the capture. A man searches for his keys under a streetlight, not because he dropped them there but because that is where the light shines. Medical research searches for genetic causes not because genes cause disease but because genetic research attracts funding. Investigating chemical causation means confronting industrial interests. Investigating genetic causation means sequencing samples in laboratories. Career incentives illuminate what is profitable to illuminate, leaving actual causes in darkness.
Rogers named another dimension of this system: biological colonialism. Traditional colonialism extracted wealth from geographic territories through force. Biological colonialism extracts wealth from human bodies through medicine. The territory being colonized is not a region but a demographic—populations with accumulated savings, retirement accounts, home equity. The mechanism is not military occupation but chronic disease. A person diagnosed with a genetic condition becomes a site of extraction: specialists, tests, therapies, medications, each generating revenue while draining assets. The diagnosis that promises answers initiates a cascade that transfers wealth from families to pharmaceutical shareholders.
The Alpha-1 Foundation’s $44 million in assets, its pharmaceutical partnerships, its genetic counseling infrastructure—this is what extraction looks like when it operates through medicine. The patient believes they are receiving care. They are being mined.
14. The Patient
A patient receives this diagnosis. They are told their condition is genetic, progressive, and incurable. They are offered testing, counseling, monitoring, and treatment. They are told their family members should be tested. They are given a phone number to call. They may be offered augmentation therapy—weekly or biweekly intravenous infusions of pooled human AAT protein, for life.
They are not told that the foundational mouse model produces healthy mice with normal lifespans. They are not told that the model’s creators acknowledge it doesn’t match human biology. They are not told that most carriers never develop symptoms. They are not told that most variants have unknown clinical significance. They are not told that standard testing produces misdiagnoses. They are not told that studies following deficient newborns for 32 years found most remained healthy.
They are told the science is settled. They are shown the volume of literature. They encounter the $44 million infrastructure designed to identify them, counsel them, and treat them. They are offered family planning guidance and prenatal testing. Their diagnosis becomes part of their medical identity, shaping every subsequent clinical encounter.
The magic trick works because no one traces the citations. The consensus appears solid because so many sources agree. What they agree on is an assumption none of them tested.
15. The Template
This essay has traced one condition through its evidentiary base. The method applies to any genetic diagnosis.
When someone receives a diagnosis framed as genetic, the evidence can be examined. What studies support the claim that this variant causes this condition? What do those studies actually demonstrate? What do they cite for their foundational assumptions? Do the citations form a closed loop? Do the papers contain admissions that contradict their conclusions? What percentage of people with the variant develop the condition? What explains the others?
The questions are not technical. They require no specialized training. They require only willingness to read what the research actually says rather than what the diagnosis implies it says.
Start with the clinical claim. Find the guideline document that supports it. Read the methodology section, not just the abstract. Identify what the authors acknowledge as limitations. Follow the citations to the animal studies. Read what the researchers admit about translation to humans. Follow the citations to the population studies. Note what percentage of carriers develop symptoms. Ask what explains the rest.
The pattern will emerge. Confident claims in patient-facing materials. Qualifying admissions in methodology sections. Citations that loop back on themselves. Assumptions that precede rather than follow from evidence.
The gap between public-facing clinical confidence and the hedged admissions within the literature is the space where the magic trick operates. The Foundation’s website declares that ZZ mutations increase lung disease risk. The research it rests on acknowledges that most carriers never develop disease, that the mouse model doesn’t match human biology, that most variants have unknown clinical significance, that testing produces misdiagnoses, that environmental factors determine outcomes.
Both cannot be true. The confident claim and the qualifying admissions are incompatible. Yet both appear in the same evidentiary ecosystem, separated only by the barrier between abstracts and full texts, between patient-facing materials and peer-reviewed methodology sections.
16. The Choice
The coming decades will see the emergence of a genetic therapy industrial complex that dwarfs current pharmaceutical sales. Gene editing, mRNA platforms, personalized genomic medicine—the infrastructure is being built now, justified by a scientific framework whose evidentiary methods this essay has examined.
The template operates identically across conditions. A disease exists. Researchers sequence DNA from affected and unaffected populations. A statistical correlation emerges. The correlation is assigned to a genomic location. The location is named a gene. The gene is declared causative. A foundation forms. Testing protocols develop. Patient registries compile data. Pharmaceutical partnerships emerge. Guidelines cite studies that cite guidelines.
At each step, ask the question: what does this evidence actually demonstrate?
When a mouse study claims to model human disease, ask: do the mice develop the condition spontaneously, or only when challenged? Do they have normal lifespans? Does their biology match human biology? What do the researchers themselves acknowledge as limitations?
When clinical guidelines cite mechanistic evidence, ask: does that evidence demonstrate causation, or correlation? Does it show the gene initiating disease, or the gene correlating with disease in people who were already sick?
When population studies report prevalence, ask: what percentage of carriers develop symptoms? What explains the rest? If environment determines penetrance, is the gene causative or incidental?
When testing is recommended, ask: what is the accuracy under blinded conditions? Can the test detect novel variants? What is the clinical significance of the result? What action follows from a positive test, and what evidence supports that action?
When the next genetic condition is announced, the same questions apply. What does the research actually show? What do the studies cite? Do the citations form a loop? What percentage of carriers develop disease? What explains the rest? What admissions appear in the methodology sections?
The framework that created alpha-1 antitrypsin deficiency as a genetic condition is not unique to this diagnosis. It is a template. Recognizing the template is the first step toward seeing through it.
The walls of the medical extraction system are concentric. Vaccination. Allopathic suppression of symptoms. Bacteriology. Virology. Genetics. Each redirects attention from environmental causes toward explanations that demand intervention while protecting industrial interests.
Genetics is the fifth wall—the innermost, the most formidable—because it presents itself as identity. Your genes feel like you. To question genetic determinism seems to question the self. Many who escape the first four walls remain trapped by the fifth. They refuse vaccines but accept genetic diagnoses. They question virology but believe their DNA is defective. They have crossed four walls only to be held by the one that feels most like truth.
But genes are not the self. They are a story told about the self—a story constructed by institutions that benefit from its telling. The evidence against this story, examined on its own terms, refutes the paradigm. What remains are the environmental factors that actually determine who gets sick: chemical exposures, nutritional deficiencies, chronic stress, electromagnetic saturation. The body responds to conditions. Change the conditions and outcomes change.
This should be impossible if disease is written in DNA. It is precisely what we would expect if the diagnosis misidentified the cause.
The Alpha-1 Foundation’s website provides a final, inadvertent admission: “Avoiding behaviors that harm the lung and liver, such as smoking or drinking alcohol, is the best way to stop or slow Alpha-1 from causing damage.”
Environment determines outcome. The Foundation says so itself.
The question is whether we will continue building diagnostic infrastructure around genetic correlations that explain nothing—or whether we will look where the streetlight doesn’t shine, toward the causes that industry prefers we not examine.
The evidence has been traced. The loop has been documented. The magic trick has been shown.
What you do with this information is not a genetic question. It is a choice.
References
Alpha-1 Foundation, Inc. and Subsidiary. Consolidated Financial Statements and Supplementary Information. Years Ended June 30, 2024 and 2023. Audited by BDO USA, P.C.
Alpha-1 Foundation. “What is Alpha-1?” and “Causes of Alpha-1.” Alpha-1 Foundation website. https://www.alpha1.org
Stoller JK, Hupertz V, Aboussouan LS. Alpha-1 Antitrypsin Deficiency. GeneReviews. University of Washington, Seattle. Created October 27, 2006; Revised June 1, 2023. https://www.ncbi.nlm.nih.gov/books/
Borel F, Sun H, Zieger M, Cox A, Cardozo B, Li W, Oliveira G, Davis A, Gruntman A, Flotte TR, Brodsky MH, Hoffman AM, Elmallah MK, Mueller C. “Editing out five Serpina1 paralogs to create a mouse model of genetic emphysema.” Proceedings of the National Academy of Sciences. 2018;115(11):2788-2793.
Meghadri SH, Martinez-Delgado B, Ostermann L, Gomez-Mariano G, Perez-Luz S, Tumpara S, Wrenger S, DeLuca DS, Maus UA, Welte T, Janciauskiene S. “Loss of Serpina1 in Mice Leads to Altered Gene Expression in Inflammatory and Metabolic Pathways.” International Journal of Molecular Sciences. 2022;23:10425.
Seixas S, Marques PI. “Known Mutations at the Cause of Alpha-1 Antitrypsin Deficiency an Updated Overview of SERPINA1 Variation Spectrum.” The Application of Clinical Genetics. 2021;14:173-194.
Foil KE. “Variants of SERPINA1 and the increasing complexity of testing for alpha-1 antitrypsin deficiency.” Therapeutic Advances in Chronic Disease. 2021;12:1-16.
Saunders DN, Tindall EA, Shearer RF, Lomas DA, Whisstock JC, Pike RN, Hayes VM. “A novel SERPINA1 mutation causing serum alpha-1 antitrypsin deficiency.” PLOS ONE. 2012;7(12):e51177.
Connolly B, Isaacs C, Cheng L, Asrani KH, Subramanian RR. “SERPINA1 mRNA as a Treatment for Alpha-1 Antitrypsin Deficiency.” Journal of Nucleic Acids. 2018;2018:8247935.
Mostafavi B, Diaz S, Piitulainen E, Stoel BC, Wollmer P, Tanash HA. “Lung function and CT lung densitometry in 37-39 year old individuals with alpha-1 antitrypsin deficiency.” International Journal of Chronic Obstructive Pulmonary Disease. 2018;13:3689-98.
Rogers T. “Biological Colonialism” and “Epistemic Capture.” Testimony before the U.S. Senate, 2025. uTobian (Substack).
Unbekoming. “The Fifth Wall: Genetics as the Final Fortress of Medical Extraction.” Lies are Unbekoming (Substack). December 2025.
Unbekoming. “Extraction: The Middle Class as Colony.” Lies are Unbekoming (Substack). November 2025.
Unbekoming. “Epistemic Capture.” Lies are Unbekoming (Substack). 2025.
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More excellent work from unbekoming, thanks for all you do.
I wonder sometimes why Big Pharma doesn’t drop the pretense and just go into the Pablo Escobar business. Of course Perdue tried and got spanked but that was because they were treading close to the CIA drug operation. Where is Lucky Luciano when you need him. Or Luigi for that matter?