Advances in Gene Therapy

Things are moving very fast in the area of gene therapy. Remember, while gene therapy that changes somatic cells is considered morally acceptable by the Vatican, any gene therapy that changes gametes is considered sinful by the Catholic Church because it corrects the defects for all subsequent generations and engineers a "better" human being (i.e., it is eugenics). 

1. Donum Vitae (1987): This document from the Congregation for the Doctrine of the Faith (CDF) teaches that techniques involving gametes (like IVF or artificial insemination) which separate the marriage act from procreation are immoral.
2. Dignitas Personae (2008): This document from the Congregation for the Doctrine of the Faith specifically outlines the church’s stance on gene therapy and stem cells, including the prohibition of procedures that manipulate or destroy embryos, including genetic engineering, cloning, and the freezing of embryos. 

Now, in practice, this is a distinction without a difference, as every parent alive would simply apply the genetic solution to their children either in utero or shortly after birth, so functionally, every subsequent generation of human beings is going to be healed of the genetic disease regardless. It's just that the Church has decided the more efficient way of doing it (gamete change) is sinful while the less efficient way (somatic cell therapy) is morally acceptable. 

HIV Cure

The Amsterdam UMC team used CRISPR-Cas gene editing—often described as molecular scissors—to target conserved (stable across strains) sequences in the HIV genome. Key findings from their 2024 work (presented ahead of the European Congress of Clinical Microbiology and Infectious Diseases):

• They employed systems like saCas9 (a smaller Cas9 variant from Staphylococcus aureus) and tested cjCas9.
• With one guide RNA (gRNA), saCas9 could inactivate HIV.
• With two gRNAs, it excised (cut out) segments of the integrated viral DNA from the host chromosome in infected T cells.
• In cell culture experiments, this led to complete elimination of infectious HIV, with no detectable viral traces or rebound. The edited cells also resisted reinfection when re-exposed to the virus.

Approved Gene Therapies (Viral Vector-Based Gene Addition or Delivery)

These deliver a functional copy of the defective gene, often using adeno-associated virus (AAV) or lentiviral vectors.

• Leber Congenital Amaurosis (LCA) Type 2 / Inherited Retinal Dystrophy due to RPE65 mutations Treatment: Luxturna (voretigene neparvovec) — in vivo AAV gene therapy injected into the eye. Outcome: Restores vision or slows vision loss; first in vivo gene therapy approved (2017/2018). Improves light sensitivity and navigation in patients with this rare blinding disorder.
• Spinal Muscular Atrophy (SMA), especially Type 1 (infantile-onset) Treatment: Zolgensma (onasemnogene abeparvovec) — in vivo AAV9 gene therapy delivering functional SMN1 gene. Outcome: One-time IV infusion; enables motor milestone achievement, prolongs survival, and reduces need for ventilation in treated infants. Approved for young children.
• Hemophilia A (severe, Factor VIII deficiency) Treatment: Roctavian (valoctocogene roxaparvovec) — in vivo AAV5 liver-directed gene therapy. Outcome: Sustained production of Factor VIII, reducing bleeding episodes and need for prophylactic factor replacement.
• Hemophilia B (Factor IX deficiency) Treatment: Hemgenix (etranacogene dezaparvovec) — in vivo AAV-based gene therapy. Outcome: Long-term Factor IX expression, significantly reducing bleeding rates.
• Duchenne Muscular Dystrophy (DMD) Treatment: Elevidys (delandistrogene moxeparvovec) — in vivo AAV gene therapy delivering a micro-dystrophin gene. Outcome: Improves muscle function and slows disease progression in eligible ambulatory patients (approved with accelerated/expanded indications).
• Recessive Dystrophic Epidermolysis Bullosa (RDEB, a severe skin blistering disorder) Treatment: Vyjuvek (beremagene geperpavec) or similar topical gene therapy. Outcome: Promotes wound healing and skin integrity by delivering functional COL7A1 gene.

Other notable approvals include therapies for aromatic L-amino acid decarboxylase (AADC) deficiency (Kebilidi) and certain immunodeficiencies like Wiskott-Aldrich syndrome (recent approvals for autologous gene-corrected stem cells).

CRISPR-Based Genome Editing Therapies (Primarily Ex Vivo)

These involve editing patient cells outside the body (ex vivo) or, in emerging cases, directly in the body (in vivo).

• Sickle Cell Disease (SCD) Treatment: Casgevy (exagamglogene autotemcel, exa-cel) — ex vivo CRISPR-Cas9 editing of hematopoietic stem cells to reactivate fetal hemoglobin (by editing BCL11A). Also Lyfgenia (lentiviral gene addition, non-CRISPR). Outcome: First CRISPR-approved therapy (UK 2023, FDA 2023). Eliminates or dramatically reduces vaso-occlusive crises (painful episodes); many patients become crisis-free with sustained fetal hemoglobin production. Functional cure in a high percentage of treated patients.
• Transfusion-Dependent Beta-Thalassemia (TDT) Treatment: Casgevy (same as above). Also earlier lentiviral therapies like Zynteglo (betibeglogene autotemcel). Outcome: Most patients become transfusion-independent with normalized or near-normal hemoglobin levels for years post-treatment.

Primary Success: OTOF-Related Deafness (DFNB9 / Auditory Neuropathy Spectrum Disorder)

• Cause: Mutations in the OTOF gene prevent proper function of otoferlin, a protein essential for transmitting sound signals from inner ear hair cells to the auditory nerve. Affected individuals are typically born profoundly deaf (or with severe hearing loss) in both ears.
• Therapy Approach: In vivo AAV (adeno-associated virus) gene therapy delivers a functional copy of the OTOF gene directly into the inner ear (usually via intracochlear injection under anesthesia). Because the OTOF coding sequence is large, some therapies use a dual-AAV vector system to split and reassemble the gene.

Key Clinical Results (as of 2025–2026)

• DB-OTO (Regeneron / Decibel Therapeutics):
  • In the pivotal CHORD trial (published in NEJM, October 2025), 12 children with OTOF-related profound deafness received a single infusion.
  • Outcomes: 11 of 12 participants (92%) showed clinically meaningful hearing improvements; 9 of 12 met the primary endpoint (average pure-tone audiometry threshold ≤70 dB HL at week 24). Three achieved near-normal or normal hearing sensitivity. Six could hear soft speech without devices. Improvements were often seen within weeks, with stability or further gains up to 72 weeks in follow-up. Some participants showed improved speech perception.
  • Regeneron has indicated plans to seek regulatory approval (potentially making this the first approved gene therapy for hearing loss).
• Other OTOF trials (China-led, Akouos/Lilly AK-OTOF, Sensorion SENS-501, and collaborations involving Harvard/Mass Eye and Ear, CHOP, etc.):
• Multiple independent trials (starting 2022–2024) restored hearing in profoundly deaf children aged 1–7 (and some older patients up to ~24 years).
• Examples: Five of six children in a bilateral treatment trial gained the ability to recognize speech, understand conversation (including in noise for some), and locate sound sources. One child went from complete deafness to mild-moderate loss and could hear voices/ambient sounds for the first time.
• Improvements often progressive over months; many achieved functional hearing sufficient to avoid or reduce reliance on cochlear implants.
• Benefits observed in both children and young adults, with rapid onset (often within 1 month) and sustained effects.

CRISPR/Gene Editing for Hearing Loss

• Preclinical/Animal Success: CRISPR-Cas9 has been used successfully in mouse models to:
  • Disrupt dominant-negative mutations (e.g., in Tmc1 "Beethoven" mice) and preserve or restore hearing.
  • Prevent progressive hearing loss or protect against noise-induced damage.
  • Improve outer hair cell survival in certain genetic models.
• Human Status: No widespread clinical success or approvals yet for CRISPR-based treatments of deafness. Early research and consensus statements note potential, but trials remain preclinical or very early-stage. One area of interest is progressive adult-onset genetic deafness (e.g., DFNA41 models), where editing showed promise in animals and patient-derived cells.

Approved Gene and Cell Therapies for Cancer

The most established successes use CAR-T cell therapy, an ex vivo gene therapy approach. Patient T cells are extracted, genetically modified (often via viral vectors) to express a chimeric antigen receptor (CAR) that targets cancer cells, expanded, and reinfused.

Approved CAR-T therapies (as of 2026) include:

• Kymriah (tisagenlecleucel): For relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) and certain large B-cell lymphomas. Many patients achieve complete remission, with some durable responses lasting years.
• Yescarta (axicabtagene ciloleucel) and Breyanzi (lisocabtagene maraleucel): For large B-cell lymphoma and other non-Hodgkin lymphomas. High rates of complete response in refractory cases.
• Tecartus (brexucabtagene autoleucel): For mantle cell lymphoma and B-cell ALL.
• Abecma (idecabtagene vicleucel) and Carvykti (ciltacabtagene autoleucel): For relapsed/refractory multiple myeloma, targeting BCMA. Significant remission rates, including stringent complete responses in heavily pretreated patients.

Other approved gene-based cancer therapies:

• Provenge (sipuleucel-T): Autologous cellular immunotherapy (gene-modified dendritic cells) for prostate cancer.
• Imlygic (talimogene laherparepvec, T-VEC): Oncolytic virus gene therapy injected into melanoma lesions to stimulate immune response.
• Adstiladrin (nadofaragene firadenovec): Adenoviral vector delivering interferon-alpha for non-muscle invasive bladder cancer.

Long-term outcomes: Some early CAR-T patients (treated around 2010) remain cancer-free over a decade later, with the modified cells persisting as "living drugs." Complete remissions have been documented in refractory leukemias and lymphomas, allowing patients to achieve durable disease-free status.

CRISPR and Gene Editing in Cancer

CRISPR-Cas9 and related editing tools (e.g., base editing) are used ex vivo to enhance immune cells or disrupt cancer-promoting genes. No broad CRISPR approvals for cancer exist yet, but clinical results are encouraging:

• CRISPR-edited CAR-T or TIL therapies: Trials show safety and responses in blood cancers and solid tumors. For example, a University of Minnesota trial using CRISPR to knock out the CISH gene in tumor-infiltrating lymphocytes (TILs) for advanced gastrointestinal cancers resulted in halted tumor growth in several patients and a complete response (tumors disappeared and did not return for over two years) in one case.
• Base-edited CAR-T (e.g., BE-CAR7): For T-cell acute lymphoblastic leukemia (T-ALL), an aggressive "incurable" blood cancer. In trials, 82% of patients achieved deep remission (enabling stem cell transplant), and 64% remained disease-free at follow-up (some over three years).
• Preclinical/early work: CRISPR to reverse chemotherapy resistance (e.g., editing NRF2 in head and neck or lung cancers) or enhance CAR-T persistence against solid tumors.

In vivo approaches (direct delivery without removing cells) are emerging, including AAV-based and lentiviral in vivo CAR-T reprogramming, with early signs of efficacy in leukemia and myeloma models.

The "non-biologist" Australian man who used AI protein-folding software to cure his dog of cancer.

Nobel Prize Winners Who Refused Judaism

It is a commonplace that Jews make up less than 1% of the world's population, but between 25% and 30% of the world's Nobel Prize winners. However, that assumes we are supposed to ignore the Nobel Prize winners' own testimony about whether or not they were/are Jewish.

A lot of them refused the title.

1. Albert Einstein (Physics, 1921) — Of Jewish descent; famously described himself as an agnostic and did not practice Judaism religiously, viewing religion more philosophically/culturally.
2. Niels Bohr (Physics, 1922) — Jewish mother (Jewish by matrilineal descent); identified as an atheist or non-religious, with no adherence to Jewish religious practice.
3. Paul Ehrlich (Physiology or Medicine, 1908) – Baptized Lutheran, moved in Christian German circles, did not consider himself Jewish.
4. Richard Feynman (Physics, 1965) — Jewish ancestry; openly identified as a positive atheist and non-believer.
5. Milton Friedman (Economics, 1976) — A prominent economist, he was an atheist/agnostic. He did not maintain religious practice. 
6. Fritz Haber (Chemistry, 1918): Despite his Jewish ancestry, Haber was a fervent German patriot who converted to Lutheranism in 1892, he portrayed himself as a German Christian patriot and actively rejected the idea that he was Jewish.
7. Herbert A. Hauptman (Chemistry, 1985) — Jewish background; grouped with nonreligious (atheist/agnostic) laureates who did not identify religiously as Jewish.
8. Roald Hoffmann (Chemistry, 1981) — Jewish heritage (survivor family); while culturally connected, often grouped with secular or non-theistic Jewish laureates.
9. François Jacob (Physiology or Medicine, 1965) — Born to a Jewish family and raised with some religious exposure; became an atheist shortly after his bar mitzvah and did not identify with Judaism.
10. Karl Landsteiner (Physiology or Medicine, 1930) — Jewish mother, baptized and raised Catholic, considered himself Catholic, actively resisted being called Jewish.
11. Élie Metchnikoff (Physiology or Medicine, 1908) — Jewish ancestry but was an atheists/agnostic who did not believe in God or practice/identify with the religion.
12. Rita Levi-Montalcini (Physiology or Medicine, 1986) — Jewish Italian family; secular/non-religious, listed among notable Jewish atheists/agnostics.
13. Jerome Karle (Chemistry, 1985) — Jewish background; identified as agnostic.
14. Harry Kroto (Chemistry, 1996) — Kroto was of Jewish descent but identified as a "devout atheist". He did not view his heritage as a defining factor of his identity
15. Boris Pasternak (Literature, 1958) — Born to an assimilated Jewish family in Moscow; parents were culturally Russian, not religiously Jewish. He was deeply embedded in Russian culture and Orthodoxy‑inflected imagery, but never converted formally.
16. Wolfgang Pauli (Physics, 1945) — Pauli’s father converted from Judaism to Roman Catholicism shortly before Pauli's birth, and Pauli was raised as a Roman Catholic. Although he later left the Church and was of Jewish descent, he did not consider himself Jewish.
17. Max Perutz (Chemistry, 1962) — Born into a Jewish family in Austria, Perutz was a baptized Catholic who later became a "devout atheist".
18. Jack Steinberger (Physics, 1988) — Born to a Jewish family; described himself as an atheist and humanist.
19. Adolf von Baeyer (Chemistry, 1905) — Often cited as the first Nobel laureate with Jewish ancestry (on his mother's side), he was baptized and raised Christian, lived as Christian German nobility and did not identify with Judaism.
20. Eugene Wigner (Physics, 1963) — Wigner’s family converted to Lutheranism when he was a teenager. While born to Jewish parents, his formal religious affiliation for most of his life was Christian.
21. Richard Willstätter (Chemistry, 1915) — Converted to Christianity, strongly identified as assimilated German, not as Jewish.
22. Many laureates from assimilated families in Germany or Austro-Hungary, like Hans Krebs, often identified primarily with German culture rather than Jewish identity

965 people have won Nobel Prizes since the establishment of the prize through 2025, only between 30 and 60 could arguably be considered to have acknowledged themselves Jews. Of those, the vast majority won either the Peace Prize or the Literature Prize.

Generally, about 220 of those individuals are considered to be Jewish, primarily due to parentage. NBut, once we exclude the people who clearly did not consider themselves Jewish (the large secular/atheist majority), the remaining group that did identify with Judaism would represent roughly 3–6% of all 965 individual Nobel laureates (or possibly lower, depending on how strictly "identify with Judaism" is defined).

Of course, less than 1% of the world's population and 3% of the Nobel Prizes is pretty good.  But this highlights a real inconsistency in how the "Jewish Nobel" statistic is often presented: it leans heavily on ethnic/heritage counting for one group while religious self-ID is used (or at least implied) for others. When we strip away ancestry-only inclusions and focus on personal identification, the Jewish share drops substantially, the atheist/secular share rises accordingly, and Christians (Catholic + Protestant + others) still dominate. 

It Is OK That No One Can Detect AI

AI is a tool that uses human-generated data, averages the data, then reproduces the average. It is a tool, just like a canvas or a paintbrush. It can produce reasonably good art and reasonably good essays because the average of its input (which generally has a strong overweight of people who write and do art for a living) is pretty good. 

The only difference between AI and a paintbrush is that AI directly mirrors our intelligence back to us. Canvas, statues, other forms of art mirror our external forms, AI mirrors back our words. 

You see in AI whatever you bring to the mirror.
If humanity frightens you, then AI is frightening.
If humanity exhilarates you, then AI is exhilarating.
If you doubt AI can be creative, then you doubt the IT bros who created the tool are truly creative.
If you see AI in other people's work, then you view everyone else's work as derivative, not truly creative, like yours is (tm). 

Your reaction to AI tells us about your reaction to other people, because that's all AI is - it's the average of the sum of other people.

You may claim that you can tell when output is AI because AI is just a synthesis of information that tends to follow a formula. But natural human responses are ALSO just a synthesis of information and these also tend to follow a formula.

That's why a computer can reliably reproduce human-sounding output. English language is actually a mathematical formula, right down to the spelling of words. Remember, AI simply converts words to numbers, runs a statistical algorithm on the numbers, gets a number string as output, then converts the number string back into words.

That's why an AI response is always grammatically correct. Grammar is really just the output of a mathematical formula. We don't realize it, but when we write sentences, we are actually doing math. We don't think of it that way, but the fact that computers can mimic us demonstrates that this is what we are doing.

When a machine produces text, it IS a human producing text, because the machine is just a tool of the human. In this sense, it is as absurd as saying, "I don't know if a human dug that hole or if a shovel dug that hole or if a backhoe dug that hole." In all three cases, a human dug the hole. Now, you know that already, but you are trying to figure out which tool was used. When we talk about AI, we talk about it as if it were already sentient - there is no reason to believe that it is sentient. It is a tool, that's all. 

Now, you may think you can detect AI generated content, but you really can't. This "I can detect AI!!" story that people tell themselves is exactly the same story university English and History profs tell themselves, because they want to continue to feel relevant and special. In 2024 research, published in PLOS ONE, researchers submitted AI-generated (ChatGPT-4) exam answers under fake student profiles to real university markers (professors/teachers) without their knowledge:

• 94% of the AI submissions went undetected as AI-generated.
• Under stricter criteria (explicitly mentioning AI), 97% went undetected.
• The AI-generated work actually received higher average grades than real student submissions.

University professors who study and use the English language to earn their bread are no better at identifying AI then you are, and they HAVE been tested against AI and human OPs. They suck at distinguishing the two, and they are supposed to do this for a living.

They hate hearing this as much as you do. For some reason, people feel like it is a personal attack to point this out. I'm not sure why. AI is just the statistical average of people, so it is the output of people one step removed.

There is no reason anyone should be able to distinguish an essay written with a spell-checker versus an essay written by someone who is naturally good at spelling. Same goes with the entire essay itself. It is not a commentary on your abilities to say you cannot distinguish the two. It is just that the people who made the spell checker or the essay generator are really good at their jobs. Why saying "Wow, they are good at what they do!" is somehow an attack on someone else is not clear to me. 

But this is the true test of your ability: can you tell if someone ran their response to you through a spell-check or a grammar-check? Both of those are just weak forms of AI. If you cannot tell whether a response was spell-checked, then you cannot tell if you are dealing with an AI response. 

You.

Cannot.

Tell. 

The Pope On War

Pope Leo's statements about war are a testimony to the failures of American Catholic education: an American pope who says "war is never holy" is apparently unaware of the reconquest of the Iberian Peninsula (711-1492), the Jerusalem Crusades (1095–1291), the Albigensian Crusades (1209–1229), the Balkan Crusades (1395-1444), the Hussite Crusades (1420–1431), or the Baltic Crusades (1170-1410).

Pope Leo likewise seems completely unaware of Pope Julius II (reigned 1503–1513), who actively commanded and led the papal army into battle, earning the nickname "The Warrior Pope" (Il papa terribile). He wore full armor, directed sieges, and fought to regain territory for the Papal States during the Italian Wars.

True, the Church also proclaimed both the Peace of God and the Truce of God, so that, by the mid-11th century, only about 80 days remained for permissible warfare, but those were both declared by bishops via local councils, not popes.

Jesus said he came to bring not peace, but a sword, to set father against son and mother against daughter. He urged his disciples to sell their cloaks and buy swords, nor did he tell them that they had misunderstood when they actually produced two swords.

Finally, even if the Iraq war is primarily about an oil grab, it is never explained why anyone should be ashamed of grabbing oil. Energy is the basic requirement for every other human need: food, clothing, clean water, shelter, and medical care. Without energy, none of those things can be used to care for others: everyone is reduced to the most abject poverty. Given that Christians are tasked with caring for the poor, securing oil is the foundational way to care for the poor in an industrialized society - a society that has already removed over 90% of the world's poverty. The Pope doesn't seem capable of grasping basic economics. 

We Are All Deists Now

The whole point of inventing programming languages was to make it possible for less skilled people to write code. When you had to write computer code in binary, hexadecimal or assembler, you had to be really, really good. Most people couldn't do it.

Programming languages removed the need to think in binary or hexadecimal. You could think using English language equivalents instead. This made programming a lot easier, thus allowing lower IQ people to code. But, allowing stupider people to code meant you not only vastly increased the number of software coders, you also vastly increased the number of defective programs. This is how software turned into the security nightmare it is today.

When AI creates computer code, it produces the statistical average of all the code out there. AI removes the bottom 50% of coders from the job. Given the Pareto principle (80% of consequences come from 20% of causes), the bottom 20% of coders were probably causing 80% of the security and integration problems. 

Since AI removes the bottom 50% of human coders, having AI produce code means most of our software security and integration problems will go away. This is likewise true in every skill area where AI is applied. 

Is AI perfect? Of course not. It makes stupid mistakes because it trains on human-generated data, which is filled with stupid human-generated mistakes. AI is just a mirror of human activity. It is us watching the average human intellect doing algorithmic work. But, once you fix an AI algorithm or a data training set, it stays fixed. Software doesn't degrade. 2+2 = 4 for all eternity, it is an equation outside of time, and that is true of every algorithm, whether AI uses it or not. 

So, AI starts at the statistical mean of every data set. It starts out being roughly as good as the average person doing the work. That means it starts out already better than half the people doing the work. 

Once you remove the bottom 50% of error-ridden data and the bottom 50% of corrupted algorithms, AI is now at the 75th percentile, not the 50th percentile. Keep iterating that process and AI quickly becomes "brilliant". That doesn't happen because AI thinks, it happens because we painstakingly work through the algorithms and the data sets, stripping out the errors and leaving only the good algorithms and data behind for AI to use and continue to train on. 

The big complaint about "science" in the last forty years is precisely that so much of it is pure crap. Endless examples of peer-reviewed published articles that aren't worth the paper they are printed on because both the researchers and the "peers" who reviewed the articles were below average in competency (and 50% of any human population is, by definition, below average). 

AI solves the problem by stripping out the bottom half. Yes, it absolutely still makes errors, but it makes a lot fewer errors than the bottom half of the human population makes. Once it is optimized, it makes fewer errors than the bottom 80%, 90%, 99%.

It used to take decades to train people to master complex tasks, master those tasks so well that even when the trained person is hung over, exhausted, sick, or otherwise incapacitated, they could still produce the necessary result. Once an AI has algorithms and data sets optimized, that information is infinitely replicable, it can now be copy-pasted into an infinite number of machines. Given a sufficiently nimble robot, i.e., a machine that can effectively interact with the environment, that means we don't have to spend decades training individual experts in a bespoke process. We can copy-paste and we have an infinite number of experts. 

The power of AI is not just in its promise of comparatively error-free operation, i.e., compared to humans, but in the instantaneous and infinite replicability of all knowledge and every technique. Teachers often crow that they "teach people how to learn". It was never really true, but now, for at least the bottom half of the human intellects in the world, it is not even necessary. Algorithms and data are now built on an assembly-line. We get the results without the work. Work literally disappears. 

In Judaism, Christianity and Islam, even God has to work in the clay of the earth to build up a human body. The AI-robotic infinite replicability of technique and knowledge means the very foundational understanding of the universe that Abrahmic religions provide will no longer correspond to the world we experience. We will all become Deists, hands-off spectators watching the tools we made produce the results we need in a clockwork universe. 

Christians believe God eternally breathes forth the single Word through which all creation comes into being: Father breathes forth Spirit and the Word. With robotic AI, we will need but to speak, and lo!, it will be made. Like God, we also will speak reality into existence, we will watch the clockwork production of our vision being built before us. Even the stupidest among us will be able to do it. Whether we want this or not, that is what we are building. 

Prenup Hypocrisy

https://www.youtube.com/watch?v=DCMkURGzcm8

The Catholic Church works very hard to avoid having anyone understand the content of the linked video above. If a couple creates and signs a prenup, the existence of that prenuptial agreement can be used later to justify an annulment in the Catholic Church. The reasoning is, that any couple who signed a prenuptial agreement weren't really serious about the "until death do us part" part. They were open to the possibility that the marriage would fail.

Keep in mind that this is unusual to marriage. Buying life insurance does not make you immediately unable to receive Anointing of the Sick, but creating and signing a prenup makes your marriage functionally invalid.

Yet, at the very same time the Church repudiates your personal prenuptial agreement, it insists that neither the marriage can be held, or the annulment proceedings begun, unless legal documents from the government are first obtained. You have to get a marriage license from the government before the Catholic Church will permit you to exchange vows and receive the graces of the sacrament. You have to get the divorce recognized by the government, and have that documentation from the government in hand, before you can start an annulment process in the Church.

Due to the way secular marriage law works, the government gives you the marriage certificate with a government-constructed prenuptial agreement. It's all part of the same document. There is literally no way around that, nor any separation between the government marriage contract and its built-in government prenuptial agreement that details what happens if the contract is later ended. 

Here's the odd part: the Church is fine with the government prenuptial agreement. In fact, the Church functionally insists you obtain the government prenuptial contract before you are permitted to exchange vows for the sacrament. In short, the Church recognizes the government's prenup, just not yours. Your marriage vows aren't good enough. The government has to recognize the vows first. Your prenup is proof that you weren't serious, but the government's pre-established prenup that you both agreed to when you got married -  your acceptance of THAT prenup is fine. You can't receive the sacrament until you get that secular, government prenup. 

As the man said, have you ever walked into the DMV and thought, "Yeah, I want these people deeply involved in how my marriage is structured." If you haven't thought that, then you aren't thinking about your marriage the same way the Catholic Church is thinking about your marriage.

Catholics MUST Accept Transsexual Marriage

So, an Argentinian priest and bishop have now forced the entire Catholic Church to recognize the validity of the sacrament of marriage between transsexuals. It was a neatly done trick. Pope Francis would be very proud. 

This is how it was done. A biological man and biological woman, each of whom presents as the other sex (man wears a dress, woman takes testosterone and tries to grow a beard), presented themselves to a friendly parish priest and asks to be married. Now, keep in mind, the couple fulfill canonical norms: marriage is between one man and one woman, that's what we have here, it's just that both are mentally unstable. But the Church has already approved the idea that such mentally unstable people can both be baptized into the Church and act as godparents for baptism or witnesses for marriage. 

So, the priest, being no man's fool, talks with his bishop, to make sure bishop was ok with it. Bishop, being no man's fool, said, "Do it, but if it comes out, you will take the fall. We will put nothing in writing, which will keep Rome off my back." Priest said, "Sounds like a plan. Deal me in." 

Now that the mockery is public, bishop announces an "investigation" and insists "there is nothing in writing that shows I approved of this." Bishop now will slow-walk the "investigation" until people stop watching, then drop it. 

Notice that at no point is anyone talking about annulling the marriage. It cannot be annulled. There are no grounds because the marriage DID fulfill canonical norms (biological woman, biological man), and  the Church presumption is always that a sacramental marriage is valid, so that has to be the presumption here.

Is the couple "open to life"? Sure. It is a biological male and a biological female, so conception could happen and the "man" could get pregnant. Heck, they may even WANT to do that so they have children to abuse. Unless either spouse contests the bond, the Church isn't going to contest - it can't. The default canonical position is ALWAYS "the bond is valid." That's canon law (1060): 

Can. 1060 Marriage possesses the favor of law; therefore, in a case of doubt, the validity of a marriage must be upheld until the contrary is proven.

You might also say, "Well, the Church cannot marry the impotent." Sure, but sexual intercourse is not necessary for a valid marriage. As long as the sexual act could be completed in principle, that's enough.  The two can be sterile - that doesn't matter. The Church has never defined what constitutes a vagina or a penis, and surgical reconstruction or "improvement" to allow for the act is certainly permissible, even encouraged, for heterosexual couples.

"It follows that any sex-change intervention, as a rule, risks threatening the unique dignity the person has received from the moment of conception. This is not to exclude the possibility that a person with genital abnormalities that are already evident at birth or that develop later may choose to receive the assistance of healthcare professionals to resolve these abnormalities." ~Dignitas Infinita, #60

The problem, of course, is what counts as "genital abnormalities." If people insist they were "born in the wrong bodies" then the presence or absence of a Y chromosome would create, in their bodies, what those very same people would insist is a "genital abnormality." The presence/absence of the offending chromosome would be a "genetic disease." Therefore, what counts as "assistance of healthcare professionals to resolve these abnormalities" is now up for grabs in a way that was never true prior to roughly this decade. No Church document addresses this. A sterile "penis" created from the muscle tissue of the forearm combined with a fake, surgically-constructed "vagina", a permanent wound that requires constant daily dilation ... well, the doctors are using the correct words, so what is the Church going to do? Say a medical doctor is wrong: that isn't a penis, that isn't a real vagina? Not likely. 

As for the sexual act itself, that is not at all necessary for validity. This lack of consummation is the basis for a Josephite marriage, which - by definition - does not ever get consummated. Remember, Josephite marriages, because the participants remain virgins, are actually superior to marriages that are consummated. 

The Result: As a Catholic you are REQUIRED to believe the marriage bond, in this instance, is valid until an annulment is declared, which it never will be. By this action, the entire Catholic Church is now bound to accept transsexual marriage. If you do not accept this marriage as valid, you are putting yourself outside the millennial-old teaching and practice of the Christ-founded Catholic Church.

If you're Catholic, you are now OK with transsexual marriage.

You're welcome.

Catholic Social Teaching: Marriage

"The women should keep silent in the churches. For they are not permitted to speak, but should be in submission, as the Law also says". 1 Corinthians 14:34-35

"I do not permit a woman to teach or to exercise authority over a man" 1 Timothy 2:12 

"Wives, submit yourselves to your own husbands as you do to the Lord. 23 For the husband is the head of the wife as Christ is the head of the church, his body, of which he is the Savior. Now as the church submits to Christ, so also wives should submit to their husbands in everything. 25 Husbands, love your wives, just as Christ loved the church and gave himself up for her (died for her)." Ephesians 5:22-25

In Catholic social teaching, the principle of subsidiarity means that decisions and actions should happen at the lowest, most local, and competent level possible. Since men carry authority over their wives, that makes men more competent than women.

Now, you might equivocate by replying "But Ephesians also says, 'Submit to one another out of reverence for Christ' so that means men have to submit to women, which makes women the authority." Incorrect. Both spouses have to submit to Christ, because God holds authority in all relationships. Men submit to women only in the sense that the woman instantiates Christ. 

"it is in her relationship with Christ—who is for both spouses the one and only Lord—that the wife can and should find the motivation for the relationship with her husband, which flows from the very essence of marriage and the family." John Paul II

That is, the woman submits to the God-man (Christ), and only in her submission to the ruler of both men and women does the man submit to her. Yet, since men are called to die for the marriage, while women are only called to submit, men are the Christological symbol in a way that women never can be.

"As children of God, man and woman have a dignity in which they are absolutely equal; and they are equal, too, in regard to the supreme end of human life, which is everlasting union with God in the happiness of Heaven. But man and woman cannot maintain or perfect this equal dignity of theirs unless they respect and make use of the distinctive qualities which nature has bestowed on each sex: physical and spiritual qualities which are indissoluble, and so coordinated that their mutual relation cannot be upset without nature itself intervening to re-establish it." Pope Pius XII

Equality of dignity, but not equality of authority or capability. Out of all of Scripture, Ephesians 5:25 is the only passage that implies men should submit to women, and that is only in reference to the reverence both spouses must have for Christ. Saying anything else is simply eisegesis, reading modern meanings into a text, forcing it to say what the reader wants it to say rather than what it actually says.

When we take the Catholic definition of subsidiarity (lowest level of competent authority) with the Scriptures (woman must submit to man), then the Church, through her God-breathed Scripture and her own commentary, recognizes men are the lowest level of competent authority. Women have equal human dignity, but are not a competent authority, whether in marriage or in any position of public authority. 

Since as "authority is understood as service, not domination", this means men excel at serving others while women are pretty crappy at serving other people. Pope John Paul II confirms this when he says: 

"He (Paul) expresses a different concept instead, namely, that it is in her relationship with Christ—who is for both spouses the one and only Lord—that the wife can and should find the motivation for the relationship with her husband, which flows from the very essence of marriage and the family."

That is, the woman has to find something which she doesn't have. Women have to be taught how to engage in service properly by a man - either Christ or her husband. The essence of marriage and the family is teaching the woman how to do what men already naturally understand how to do.

This may explain why women have historically been put in service roles, thus providing them with the necessary practice at serving that men have as an in-born trait. Or, to put it another way, there is truth in the old saying, "A man will sacrifice his happiness for his family, while a woman will sacrifice her family for her happiness." Women must train themselves, or be trained, into imitating the man (husband or Christ) instead of following her own inborn inclinations. In fact, women are so unsuited to taking care of anyone but themselves (and arguably, even that is at issue) that not only are women not the source of authority in the ordo of marriage, women cannot even be considered for ordination into divine orders of service: deacon, priest or bishop. 

TLDR: Men are competent in handling a marriage, women are not.

Most Western cultures used to reflect this understanding by forbidding women from initiating divorce. As Western culture stopped being Christian, this Christian wisdom disappeared from the culture. Thus, women can and do initiate 70% of intimate partner violence, and between 70% and 90% of divorces. Of the three different possible pairings, studies show lesbian couples have the highest level of divorce and strife. Not surprising, given the couple is composed of two completely incompetent people.

Scripture = science = Christian teaching.

This isn't hard for men to understand, but women find it impossible to grasp, thus demonstrating the principle.