Biotechnologie
Klonierte Dire-Wölfe: Biotechnologischer Durchbruch definiert das Aussterben neu
Wissenschaftliche Auferstehung
Even before the dawn of civilization, many species went extinct, usually from a mix of climate warming at the end of the Ice Age, and over-hunting or competition with early human populations.
Als dies „nur“ vor 10.000 Jahren geschah, bedeutet das, dass diese kürzlich ausgestorbenen Arten Überreste hinterlassen haben, besonders in kalten Regionen, mit noch wiederherstellbarer DNA. Während also die Jurassic‑Park‑Idee, Dinosaurier‑DNA zu finden, wahrscheinlich Science‑Fiction bleibt, könnten einige ausgestorbene Arten potenziell wiederbelebt werden.
Und genau das soll ein Biotech‑Unternehmen namens Colossal Biosciences erreicht haben – mit einer ausgestorbenen Wolfsart: dem Dire‑Wolf.
Das Tier ist seit 12.500 Jahren ausgestorben und wurde dank seiner zentralen Rolle in G.R.R. Martins Fantasy‑Geschichte und der HBO‑Serie Game of Thrones zu einem populären „mythischen“ Tier.
Natürlich erkannte Colossal das PR‑Potential und ließ die frisch „auferstandenen“ Dire‑Wolf‑Welpen mit dem berühmten Autor fotografieren und benannte einen der Wölfe nach einer Figur aus den Büchern.
“Wir haben drei Dire‑Wolf‑Welpen gemacht. Es gibt Romulus und Remus, die fünf Monate alt und etwa 80 Pfund schwer sind. Sie sind wunderschön.
Dann gibt es Khaleesi, etwas über sechs Wochen alt. Sie ist ein Baby, unser erstes Mädchen.”
Doch sind diese Tiere wirklich Dire‑Wölfe? Und was bedeutet das für die Zukunft des Naturschutzes sowie für andere ambitionierte Pläne von Colossal, als nächstes das Wollhaarmammut wiederzubeleben?
Dire-Wölfe
Vielleicht das Überraschendste an den Dire‑Wölfen ist, dass sie technisch gesehen keine Wölfe sind. Obwohl sie zur Familie Canidae und zur Untertribus Canina gehören, bilden sie eine eigene Gattung: Aenocyon (bedeutet „schrecklicher Hund“), während „normale“ Wölfe zur Gattung Canis gehören.
Quelle: Thallaso Atrox
Der Dire‑Wolf war etwa so groß wie die größten modernen Grauwolf‑Formen und manchmal sogar größer, mit einigen einzigartigen morphologischen Merkmalen: kleineren Pfoten, größerem Kopf, vermutlich Anpassungen an die Jagd auf die arktische Megafauna jener Zeit.
Dieser größere Kopf und die größeren Zähne verliehen dem Dire‑Wolf eine Beißkraft, die 20 % stärker ist als die selbst der stärksten heutigen Wölfe und Hunde.
Quelle: The Armory
Während die Ursache ihres Aussterbens umstritten ist, besteht der wissenschaftliche Konsens darin, dass sie aus einer Kombination von Klimawandelwirkungen und Konkurrenz mit anderen Arten resultierte, einschließlich Überjagung durch neu in Nordamerika ankommende Menschen.
Colossal-De-Extinktion-Prozess
Ziele der De-Extinktion
Die Rückkehr des Dire‑Wolfes oder einer dire‑wolf‑ähnlichen Kreatur (mehr dazu im folgenden Streit) ist nicht die erste genetische Ingenieurleistung von Colossal.
A month prior, the company released news of the newly created “wooly mouse”. These test mice received seven different genes coding for the woolly mammoth’s wooliness through a complex and very advanced multiplexed genome engineering technique.
Quelle: IFL Science
Diese genetischen Manipulationen betreffen nicht nur den oberflächlichen ästhetischen Aspekt des Fells, sondern auch die Kälteresistenz und Änderungen im Lipidstoffwechsel des Tieres, die erforderlich sind, um einen tropisch lebenden Elefanten in einen arktisch lebenden „de‑extinkten“ Mammut zu verwandeln.
Quelle: IFL Science
Colossal war außerdem zuvor an einem Versuch beteiligt, das Aussterben der Rotwölfe zu verhindern, von denen nur noch 16 in freier Wildbahn leben, alle in einem ländlichen Fünf‑County‑Gebiet im Nordosten von North Carolina. Allerdings ist die Tatsache, dass diese Tiere eher Kojoten‑Rotwolf‑Hybride als „echte“ Rotwölfe waren, unter Naturschützern umstritten.
Wie es funktioniert
Die Grundidee der De‑Extinktion besteht darin, die DNA der ausgestorbenen Art zu analysieren und mit noch lebenden, eng verwandten Arten zu vergleichen.
“Colossal has de-extincted the dire wolf. We took a 13,000-year-old tooth, a 74,000-year-old skull, and made puppies, and then we also used some of that same tech to help save the red wolves, which is really exciting.”
- Wiederherstellung der Schlüsselfunktionen, die der ausgestorbenen Art ihre einzigartigen Merkmale verliehen.
- Unterstützung der zurückgeholten Art, sich an die aktuellen Umweltbedingungen anzupassen und zu überleben, mittels weiterer genetischer Modifikationen.
- Entwicklung von Resistenz gegen Krankheiten und andere Bedrohungen, um die Art in der Natur lebensfähig zu machen.
Quelle: Colossal
Dies erfordert mehr als nur genetisches Engineering, auch wenn es das Kernstück des Projekts ist, wobei CRISPR‑Cas9 das wichtigste Werkzeug für Colossal darstellt.
Das Unternehmen muss außerdem KI & Machine Learning korrekt einsetzen, um sehr komplexe biologische Daten zu verarbeiten, was es künftig in anderen Bereichen monetarisieren möchte.
In addition, good handling of embryology (the science of embryo development) is required to successfully implant the modified eggs in the “surrogate” mother that will carry to term the new species, be it wolf or elephant.
Kehrt es das Aussterben um?
Biologists and conservationists worldwide are debating if what Colossal is doing is really useful or even at all bringing back dead species.
The core of the issue is the definition of a species. In the early era of biological sciences, any animal looking like a given species (phenotype) would have been considered as part of that species. However, a modern understanding of genetics makes it clear that the genetic diversity of another species is much greater than just looks.
So while 20 genetic differences identified by Colossal can make the new puppies look like dire wolves, from a genetic point of view, they are just gray wolves looking like dire wolves, not “real” ones.
“Ancient DNA is like if you put fresh DNA in a 500-degree oven overnight. It comes out fragmented – like shards and dust. You can reconstruct it, but it’s not good enough to do anything else with.
The animals are “genetically modified gray wolves. So what Colossal has produced is a gray wolf, but it has some dire wolf-like characteristics, like a larger skull and white fur.”
Still, these criticisms ignore that this is a major achievement and that, ultimately, even more genetic diversity could be achieved through that technology.
Warum De‑Extinktion versuchen?
Colossal is very much looking to draw a parallel to the Apollo mission, claiming their de-extinction efforts are just a stepping stone in a much larger and more impactful revolution from genetic engineering.
Like the Apollo program, the scientific efforts at Colossal make ongoing contributions to the scientific community. Today, we too are within reach of another massive scientific breakthrough, one that will create a positive impact on the long-term health of Earth and its inhabitants, both past and present, as we look forward to rewilding the future.
However, these ambitious goals do not answer the question of what to do with newly resurrected species (or invented depending on the definition you use). Should they be released in the wild, without knowing the benefits or risks it could cause the affected ecosystems and local species?
At least for now, the focus of the company on large animals means that any mistake could likely be solved by hunting them down. However, the same technology applied to insects, marine animals, or plants could cause untold and irreversible ecological damages, akin to introducing invasive species to new habitats.
Another source of ecosystem variety stems from our new technologies to de-extinct lost genes, including deep ancient DNA sequencing, polyphyletic trait analyses, multiplex germline editing, and cloning. The dire wolf is an early example of this, including the largest number of precise genomic edits in a healthy vertebrate so far. A capability that is growing exponentially.
George Church, Ph.D. / Colossal Co-Founder
Zukünftige Anwendungen
Wiederbelebte Arten
So far, Colossal seems focused chiefly on resurrecting the woolly mammoth as the emblematic project of the company.
Colossal analyzed 59 woolly, Columbian, and steppe mammoth genomes ranging from 3,500 to over 1.2 million years old, and used computational analysis to compare a data set of 121 mammoth and elephant genomes, including the high-quality reference genomes for Asian and African elephants the company previously created.
It could also turn into an interesting business model for the company, allowing it to raise mammoth for tourism or even meat production perspective, a monopoly on which it could likely ask for premium prices.
Quelle: Colossal
Other species are also in plan, notably the dodo birds and the Tasmanian wolf / Tasmanian tiger / Thylacine.
However, it is likely that, to some extent, the dire wolf and the mammoth projects are essentially just learning experiences and PR for Colossal.
The company’s scientific push is led by George Church, who was a pioneer in genomic sequencing methods, chip-based DNA libraries, genome editing, and stem cell engineering.
Verbesserung bestehender Arten
The way elephants can be adapted to live in cold climates, cattle, and other farm animals, as well as crops, could be adapted through genetic engineering for higher yields or better resilience.
Colossal’s four primary labs are already working on such themes, as they are targeting “precision livestock solutions” and sustainable agriculture practices.
Quelle: Colossal
In the long term, this concept could be pushed even further to engineer de-facto new species for specific human purposes. For example, neo-species could produce silk proteins in plants or in animal fur, human medicines in fruits, etc.
Bioengineerte Entschmutzung
Colossal is also looking into the potential of plants and other organisms to reduce pollution. This includes environmental remediation, but also plastic-eating bacteria, with a spin-off company previously incubated at Colossal’s labs: Breaking.
In collaboration with Harvard / Wyss Institute, Breaking engineered MICROBE X-32™, which could potentially speed up the degradation of all existing types of plastic.
Biotech‑Werkzeuge
In order to succeed in creating the dire wolf and maybe the mammoth, Colossal needed better bioinformatics tools, notably for processing and interpreting large-scale biological data.
They also push further the technology of DNA barcode multiplexing, which allows for the simultaneous identification of multiple genetic markers.
Medizin‑ & In‑Silico‑Werkzeuge
Colossal has applied its expertise in CRISPR-Cas9 gene editing to create better disease models in animals and cell cultures, which are useful for researchers and speed up medicine development.
This includes gene therapy using a virus (AAV) as a vector, with a company spun off from Colossal to commercialize the progress on this technology, FormBio. FormBio uses AI and machine learning for cell and gene therapy candidate validation and makes manufacturing AAV medicine more efficient and accessible.
Regenerative medicine could also benefit from the company’s discoveries in embryology and in vitro fertilization (IVF), which could lead to applications in tissue engineering, stem cell research, and organ transplantation.
Fazit
Beyond the debate arguing if Colossal’s dire wolves are a true resurrection of an extinct species or the wisdom of releasing such creatures in the wild, the technological achievement of the company is impressive.
Between dire wolves and woolly mice, they seem to be able to somewhat routinely modify the genome of animals in double-digit locations, radically changing their metabolic activity and body structure.
This ability will likely have tremendous applications in other fields, with husbandry and farming the most obvious candidates.
Beyond animal modification, the technology used here can be deployed to bioengineer new plants, microbes, and other organisms to solve specific issues, like, for example, plastic pollution.
In the process, Colossal has also developed a powerful tech stack of viral vectors, bioinformatic solutions, AI & machine learning, and cell manipulation that could be deployed to many other sectors, from gene therapy to disease models and organ transplantation.
