SpaceX AND BioX Do It Again!!

“In science one tries to tell people, in such a way as to be understood by everyone, something that no one ever knew before. But in poetry, it's the exact opposite.

--Paul Dirac (1902-1984)

                                                                 

Backstory: Yup. SpaceX did it again. They landed a rocket booster on a bullseye; even catching it in the air with large mechanical arms they called “chopsticks.” The Brewers would love to have an outfielder like that!

BioX also did it again, following its last year’s Nobel Prize win for the mRNA technology that led to the very effective COVID vaccines. Just a few days before the SpaceX catch, it was announced that BioX won the 2024 Nobel Prize for using a computer, or artificial intelligence, to decipher the structure of ALL known proteins, and for using similar technology to create whole new functional proteins that promise to remediate environmental contamination and treat diseases. We are in a new brave world of science.

For those new to these pages, “BioX” is what I earlier dubbed the new, post-molecular biology (mobio) science that has been absolutely amazing. And I speak as a molecular biologist who now feels like a scientific dinosaur. What we learned from the old-school mobio is now being fed into computers which do all the work for us. Much tedious lab work has now become obsolete, which means that we are learning about our bio-world at an unbelievable pace. It also means that we are translating all that information into useful tools, such as better vaccines and medicines, and into making new proteins that do what we wish—like digest plastics contaminating our environment.

The science of molecular biology began in the 1920s with really basic questions. Swedish chemist and Nobel Prize winner, Theodor Svedberg, developed the ultracentrifuge in 1924, which was then used to determine the size of biomolecules—the first major question in molecular biology. The centrifuges were also used to separate different cell components, which played a huge role in discovering how cells function. The ultracentrifuge was a major tool used by only a few of the most advanced labs at that time. Now, pretty much every bioscience department has at least one ultracentrifuge.

Three decades after the advent of ultracentrifuges, Jim Watson, an American, and Francis Collins, a Brit, at Cambridge University, reported on their seminal discovery of the structure of DNA, which unleashed a storm of research into how it functions and deciphering the genetic code. That in turn led to much research into the other nucleic acid molecules found in cells, RNA. And that guided research into the structure and function of proteins, the things that make cells function. All that mobio research led to many, many Nobel Prizes. All that information provides the basis for the new post-mobio science of BioX.

Current story: All this background is mentioned in order to introduce the latest Nobel Prize for Chemistry, announced October 8. Three BioX chemists share the award. Demis Hassabis and John Jumper of Google DeepMind used AI to decipher the structure of millions of proteins. David Baker of the University of Washington used similar computer software to invent new proteins. It is possible that none of them ever purified DNA from a cell culture, sequenced DNA, cloned a gene, inserted a gene into cells to determine its function, etc. All of that is mobio—old stuff. These post-mobio scientists showed us we really do not need to that anymore if you can use a computer. Boy, does that make me feel old.

It used to take decades and many thousands of dollars of high tech equipment and an army of lab techs, students and post-docs to learn how a single protein, like hemoglobin, was structured and functioned. Now it takes minutes and a lap top. Computers can be used to predict the structure of any protein in the human body, which can inform researchers how other molecules will bind or physically attach to it. This is the new path for drug discovery.

These are the 2024 BioX Nobel Prize winners:

Demis Hassabis was born in London, where his parents—one a Greek Cypriot, the other Singaporean—ran a toy store. At one time, he was the second-highest-ranked chess player under 14 in the world. He began designing video games professionally before attending college. After completing a computer science degree at the University of Cambridge, he founded a video game company then returned to academia for a PhD in neuroscience. He and a fellow academic, Shane Legg, and a childhood friend, Mustafa Suleyman, founded an AI start-up called DeepMind in 2010. About four years later, Google acquired it for $650 million.

DeepMind’s goal was to build an artificial machine that can do anything the human brain can do. It also explored other technologies that could solve particular scientific problems. One of those technologies was AlphaFold, the program used to solve the structure of millions of proteins and for which the Nobel Prize was awarded. AlphaFold is built using a mathematical system called a neural network. With neural networks, computers can analyze vast amounts of data to learn to perform many tasks that were once beyond their capacity.

John Jumper, the youngest chemistry laureate in over 70 years, was born in the United States. After finishing an undergraduate degree at Vanderbilt University and a master’s degree at the University of Cambridge, he earned a Ph.D. degree in theoretical chemistry at the University of Chicago.

He joined Hassabis at DeepMind as a researcher in 2017 after Google had acquired the technology. He soon began work on AlphaFold. In 2020, Google researchers unveiled an update of the AlphaFold technology and showed that it had fully cracked the problem of predicting shapes of proteins with an accuracy that rivaled physical experiments and made lab rats like me obsolete. Sigh....

With AlphaFold, the Google team was able to calculate the structure of all human proteins, and then, according to the Nobel committee, it deciphered “the structure of virtually all the 200 million proteins that researchers have so far discovered when mapping Earth’s organisms.” Holy moly!!

David Baker’s work preceded the emergence of these AI models and focused on creating novel proteins. A Seattle native, Baker earned his undergraduate degree from Harvard in 1984 and in 1989, a biochemistry PhD from the University of California, Berkeley. He now serves as the director of the Institute for Protein Design and is a professor of biochemistry at the University of Washington (the other UW). In 2003, Baker and his colleagues created the first entirely new protein: a molecule called Top7. The molecule was useless but symbolic.

Since then, the researchers have used a computer model called Rosetta, which searches databases of existing proteins to find a sequence that might create a desired structure. Baker realized that if he could create a novel protein structure, he should also be able to create proteins “that actually do things,” like break up the amyloid fibrils that are thought to cause Alzheimer’s disease. Or digest plastic bottles. Or oil contamination from spills.

So far, his lab’s novel proteins—created with a more advanced iteration of Rosetta—have already been the basis of several potential medical treatments, like an antiviral nasal spray for Covid-19 (on which I will soon blog) and a medication for celiac disease. A Covid-19 vaccine, SKYCovione, based on his one of his lab’s proteins, was approved for use in South Korea in 2022.

Baker is also a co-founder of more than 20 biotechnology companies.

Congratulations, BioX! Stay tuned, more is sure to come.

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