#12 | World’s First Genetically-Edited Pig Kidney Transplant

Quote of the Week 💬 

World’s First Genetically-Edited Pig Kidney Transplant

⌛ The Seven Second Summary: Researchers at the Massachusetts General Hospital conducted what is believed to be the world's first successful transplant of a genetically-edited pig kidney into a human.

🔬 How It Was Done:

• A pig kidney was identified and received 69 genomic edits using CRISPR-Cas9 technology for the following purposes:

  • Inactivate a type of virus that is naturally found in the genomes of pigs to eliminate the risk of infection in the donor recipient.

  • Remove specific pig genes that produce sugars capable of triggering an immune system response in a human body.

  • Add specific human genes to improve the kidney’s overall compatibility with a human body.

• Afterwards, the donor patient underwent a 4-hour surgery where their kidney was replaced with the pig donor’s.

💡 Why This May Matter: There is already a worldwide organ shortage, and kidneys are by far the most common organ needed for transplant, according to the United States’ Organ Donor. This milestone suggests we may not be too far from a future where gene editing technologies and other emerging solutions are utilized to increase the supply of compatible organs for people in need of a transplant.

🔎 Elements To Consider: It is unclear how long this pig kidney will remain compatible in the donor recipient before complications emerge; it could be as soon as a few weeks or as long as several years. Regardless of the duration, there will be much to learn from this story in order to pave the way for future innovations in organ transplantation.

📚 Learn More: Mass General Hospital.

Stat of the Week 📊 

FDA Approves Gene Therapy For Kids With A Debilitating Disease

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⌛ The Seven Second Summary: The U.S. Food & Drug Administration announced the approval of its first gene therapy to treat children with metachromatic leukodystrophy.

🔬 How It Was Done:

• Metachromatic leukodystrophy is a rare and debilitating genetic disease affecting the brain and nervous system.

• It is caused by a deficiency of a specific enzyme that leads to a buildup of fatty substances in cells. An accumulation of this buildup damages a person’s central and peripheral nervous system, which results in a loss of motor and cognitive function.

• To administer the therapy treatment, blood stem cells are taken from the patient, genetically modified to include functional copies of the gene responsible for the deficient enzyme production in their body, and transplanted back into the patient so the stem cells can multiply within their bone marrow.

🧮 Key Results:

• In a study involving 37 children, 100% of children who were treated with a single dose of this gene therapy were alive at 6 years of age, compared to only 58% of untreated children.

• Furthermore, 71% of children treated with the gene therapy were able to walk without assistance at 5 years of age, and 85% had normal language and performance IQ scores. While similar data was not released about children from the untreated control group, it is already known that kids with this disease typically begin to lose the ability to walk and talk around age 2.

💡 Why This May Matter: As a result of this approval, it is now possible for a baby to be diagnosed and treated for this disease before they show any physical or cognitive symptoms. If there is an early enough intervention, the hope is this treatment will not only prolong the child’s life but also significantly improve the quality of their life. There may soon be cases of children who grow to live relatively healthy adult lives, which was unheard of prior to this treatment.

🔎 Elements To Consider: The wholesale price of this lifesaving therapy is $4.25 million USD. It is now the world’s most expensive drug, which means public and private action will surely be taken to ensure the treatment remains accessible for children in need.

📚 Learn More: FDA.

AI x Science 🤖

A Method To Mix & Match AI Models Together

Sakana AI shared the results of their efforts to build a model merging method to improve the performance of large neural network models. They iteratively combined, tested and evolved smaller models together to design new, more performant models.

For example, they created EvoLLM-JP with this approach, which is a Large Language Model with 7 billion parameters and fine tuned to complete math problems. In a benchmark test of grade school math problems, EvoLLM-JP was 36% - 55% accurate compared to a 50% accuracy rate of Chat GPT-3.5, the next best model tested. Interestingly, EvoLLM-JP outperformed some models 10x its parameter size, which showcases its efficiency improvements.

The researchers also created two other models, and they both performed at state-of-the-art levels in their respective domains during benchmark tests. One model was designed to generate images. The other model was designed to answer questions about images.

While this is not an entirely novel model design approach, it is meaningful to see researchers stitch together specific components of other open source models to build more efficient and capable systems. There are over 500,000 open-source models on HuggingFace alone, and most of these models are optimized for a specific domain or architecture. If researchers continue to explore new ways to mix and match the best parts of these models together, they may discover new breakthroughs in how to build AI systems with far more intelligent processing, understanding and reasoning capabilities. Sakana AI. arXiv. Github.

Our Full AI Index

• Cancer Predictions: An international team of researchers developed an AI system to predict which breast cancer patients may be at risk of side effects after surgery and radiotherapy. In a data set of 6,361 breast cancer patients, the model demonstrated an overall predictive accuracy of 73.4%, and is scheduled for clinical trial tests throughout Europe at the end of the year. University of Leicester. PRE-ACT.

• Multimodal AI Models: Researchers at Apple have been trying to figure out the best way to build AI models to understand both images and text, and they shared what they learned from a variety of experiments they conducted. They discovered the image resolution and the size of their encoder were the most impactful components of their model’s overall performance. Furthermore, when they made their models really big, their performance became state-of-the-art after viewing just a few examples. Their models also demonstrated reasoning abilities over multiple images, explained its own outputs and read texts contained within images. arXiv.

• Brain Image Reconstruction: After a single 1 hour session of fMRI brain scanning, researchers from the Medical AI Research Center successfully used their machine learning model to reconstruct high-quality images from what their patient’s brain activity was visualizing, such as a cat, bus or vase of flowers. Previous models required 40 hours of training data to produce similar results, indicating a 97% reduction in training data to generate best-in-class results. MindEye2. Github. arXiv.

• Drug Development: A company developed an AI system to help researchers design a candidate drug for the lung disease, idiopathic pulmonary fibrosis. The AI suggested a specific protein to target to treat the disease, as well as the drug’s chemical structure to interact with the targeted protein most effectively. The drug has since advanced to Phase II clinical trials, where the AI-inspired drug’s safety and efficacy will be measured in humans. MIT Tech Review. Nature.

• Policy: Tennessee became the first U.S. state to sign legislation to protect musicians from unauthorized AI impersonation. The law takes effect on July 1st. NPR.

Other Observations 📰

Woman Given A New 3D-Printed Windpipe

Researchers at the St. Mary’s Hospital in Seoul, South Korea conducted what is believed to be the world's first successful transplant of a 3D-printed windpipe into a human.

Many steps were required to build a compatible device in this manner. First, nasal stem cells and cartilage cells were procured and prepared for bioprinting. Once these cells were combined with other vital components to create the bio-ink for the printer, the researchers used this material to produce functional, tissue-like structures of an artificial windpipe.

After completing this step, CT and MRI scans were used to design a replica of the patient’s windpipe. This is an intricate design to reproduce, because the 3D printed material needed to match the precise shape, size and contours of the patient’s actual windpipe in order to fit inside their respiratory system like a missing puzzle piece.

Once the artificial windpipe was 3D printed, it was refined using biodegradable materials and other post-production processes before it was used in the transplant surgery. Since the final product is biodegradable, it is only expected to last for 5 years. However, the scientists hope the structure of the artificial organ will help the patient’s body regenerate their own windpipe during this time.

What an incredible display of innovation. It is all the more fitting to have the news of this procedure occur around the same time as the pig kidney transplant story we featured earlier. The future is getting brighter by the day for patients in need of tissue and organ transplants. BBC Science Focus.

Our Full Science Index

• Energy: The CEO of BYD recently mentioned sales of battery electric vehicles and plug-in hybrids will soon make up more than half of all new cars sold in China. The country’s transition to renewable energy is taking shape at a staggering pace, which is a welcome sign because China is by far the world’s largest energy consumer and carbon emitter. The Driven.

• Cancer Screening: A large scale study of 7,861 patients across 265 U.S. facilities measured the efficacy of a blood test to screen for colorectal cancer. The researchers found this test had a 83% sensitivity for colorectal cancer, a 90% specificity at identifying advanced neoplasia, and a 13% sensitivity at identifying advanced precancerous lesions. These results are comparable to the performance of existing screening methods, which is significant because effective screening methods have played a crucial role in steadily improving cancer survival rates over time. NEJM Study. 

• Brain-Computer Interface: The Wall Street Journal reported on the work of Precision Neuroscience, a brain–computer interface company developing a device striving to help patients with paralysis operate digital devices using their thoughts. This comes on the heels of a livestream Neuralink video, where a patient demonstrated how they were using the technology to play chess and online video games. Wall Street Journal.

• Space: The Oregon Outback Dark Sky Network has completed its first phase of a large project to establish a landscape-level international dark sky sanctuary. This first phase certified a 2.5 million-acre area in the southeastern part of the state, which now makes it the largest dark sky zone in the world. Once all phases are complete, the project will encompass over 11.4 million acres of protected night skies. Dark Sky.

• Policy: The U.S. Environmental Protection Agency announced its final ruling to prohibit uses of chrysotile asbestos. Asbestos is a known carcinogen and this specific type of asbestos is the only known form that is still used in or imported to the U.S. EPA.

Media of the Week 📸 

A Human-Sized Robot Performs A Backflip

Our long-time subscribers may have noticed we like to feature videos of robots with impressive displays of dexterity or autonomy. This video is no exception. It caught our eye because it’s showcasing a humanoid robot performing a physical task that we cannot do ourselves. This is still rare to see in 2024. Do you think it will still be rare in 10 years?

Human Brains Preserved Up To 12,000 Years Old

Researchers from the University of Oxford compiled the records of over 4,000 ancient human brains. These records contain preserved brain samples spanning 6 different continents from as far back as 12,000 years ago. University of Oxford. Royal Society Publishing.

This Week In The Cosmos 🪐

No major events this week?! 😱