Biology to the Rescue

I feel much about synthetic biology as I do AI: I don’t really understand it from a technical point of view, but I sure am excited about its potential. Sometimes they even overlap, as I’ll discuss later. But I’ll start with some recent developments with bioplastics, a topic I have somehow never really covered.

If you always thought biology was boring, you're not paying enough attention. Credit: Bing Image Creator

Let’s start with some work at Washington University (St. Louis) involving, of all things, purple bacteria. In case you didn’t know it – I certainly didn’t – purple bacteria “are a special group of aquatic microbes renowned for their adaptability and ability to create useful compounds from simple ingredients,” according to the press release. The researchers are turning the bacteria into bioplastic factories.

One study, led by graduate student Eric Connors, showed that two “obscure” species of purple bacteria can produce polyhydroxyalkanoates (PHAs), a natural polymer that can be purified to make plastics.  Another study, led by research lab supervisor Tahina Ranaivoarisoa, took another “well studied but notoriously stubborn” species of purple bacteria to dramatically ramp up its production of PHAs, by inserting a gene that helped turn them into “relative PHA powerhouses.” The researchers are optimistic they could use other bacteria to produce even higher levels of bioplastics.

Purple bacteria at work. Credit: Joe Angeles/WashU

The work was done in the lab of associate professor Aripta Bose, who said: “There’s a huge global demand for bioplastics. They can be produced without adding CO₂ to the atmosphere and are completely biodegradable. These two studies show the importance of taking multiple approaches to finding new ways to produce this valuable material.”

“It’s worth taking a look at bacteria that we haven’t looked at before,” Mr. Conners said. “We haven’t come close to realizing their potential.” Professor Bose agrees: “We hope these bioplastics will produce real solutions down the road.”

Meanwhile, researchers at Korea Advanced Institute of Science and Technology, led by Sang Yup Lee, have manipulated bacteria to produce polymers that contain “ring-like structures,” which apparently make the plastics more rigid and thermally stable.  Normally those structures would be toxic to the bacteria, but the researchers managed to enable E. coli bacteria to both tolerate and produce them.  The researchers believe that the polymer would be especially useful in biomedical applications, such as drug delivery.

As with the Washington University work, this research is not producing output at scale, but the researchers have good confidence that it can. “If we put more effort into increasing the yield, then this method might be able to be commercialized at a larger scale,” says Professor Lee. “We’re working to improve the efficiency of our production process as well as the recovery process, so that we can economically purify the polymers we produce.”

Because the polymer is produced using biological instead of chemical processes, and is biodegradable, the researchers believe it can be important for the environment. “I think biomanufacturing will be a key to the success of mitigating climate change and the global plastic crisis,” says Professor Lee. “We need to collaborate internationally to promote bio-based manufacturing so that we can ensure a better environment for our future.”

Environmental impact is also very much on the minds of researchers at the University of Virginia. They are working on creating biodegradable bioplastics from food waste. “By creating cost-effective bioplastics that naturally decompose, we can reduce plastic pollution on land and in oceans and address significant issues such as greenhouse gas emissions and economic losses associated with food waste,” said lead researcher Zhiwu "Drew" Wang.

The team is developing microorganisms that convert food waste into fats, which are then processed into bioplastics. Those bioplastics then should easily be composed. “Our first step is to make single-layer film to see if it can be utilized as an actual product,” said Chenxi Cao, a senior in packaging and system design. “If it has good oxygen and water vapor barriers and other properties, we can move to the next step. We aim to replace traditional coated paper products with PHA. Current paper products are often coated with polyethylene or polyactic acid, which are not fully degradable. PHA is fully biodegradable in nature, even in a backyard environment.”

The approach is currently still in the pilot project stage.

If all that isn’t cool enough, our own bodies may become biofactories, such as to deliver drugs or vaccines. Earlier this year researchers at UT Southwestern reported on “in situ production and secretion of proteins,” which in this case targeted psoriasis and two types of cancer.

The researchers say: “Through this engineering approach, the body can be utilized as a bioreactor to produce and systemically secrete virtually any encodable protein that would otherwise be confined to the intracellular space of the transfected cell, thus opening up new therapeutic opportunities.”

“Instead of going to the hospital or outpatient clinic frequently for infusions, this technology may someday allow a patient to receive a treatment at a pharmacy or even at home once a month, which would be a significant boost to their quality of life,” said study leader Daniel Siegwart, Ph.D. Professor Siegwart believes this type of in situ production could eventually improve health and quality of life for patients with inflammatory diseases, cancers, clotting disorders, diabetes, and a range of genetic disorders.  

I promised I’d touch on an example of synthetic biology and AI overlapping. Last year I wrote about how “organoid intelligence” was a new approach to biocomputing and AI. Earlier this year Swiss firm FinalSpark launched its Neuroplatform, which uses 16 human brain organoids as the computing platform, claiming it was: “The next evolutionary leap for AI.”   

“Our principal goal is artificial intelligence for 100,000 times less energy,” FinalSpark co-founder Fred Jordan says.  

Four clusters of living neurons are connected to electrodes on Neuroplatform/ Credit: FinalSpark

Now FinalSpark is renting its biocomputers to AI researchers at several top universities…for only $500 a month. “As far as I know, we are the only ones in the world doing this” on a publicly rentable platform, Dr. Jordan told Scientific American. Reportedly, around 34 universities requested access, but FinalSpark so far has limited use to 9 institutions, including the University of Michigan, the Free University of Berlin, and the Lancaster University in Germany.

Scientific America reports related work at Spain’s National Center for Biotechnology, using cellular computing, and at the University of the West of England, using – I’m serious! – fungal networks. “Fungal computing offers several advantages over brain-organoid-based computing,” Andrew Adamatzky says, “particularly in terms of ethical simplicity, ease of cultivation, environmental resilience, cost-effectiveness and integration with existing technologies.”

Bioplastics, biofactories, biocomputing -- pretty cool stuff all around. I’ll admit I don’t know where all of this is leading, but I can’t wait to see where it leads.   

Tiny Is MIghty

I am a fanboy for AI; I don’t really understand the technical aspects, but I sure am excited about its potential. I’m also a sucker for a catchy phrase. So when I (belatedly) learned about TinyAI, I was hooked.  

The future is tiny -- TinyAI. Credit: Nakhle/Cell

Now, as it turns out, TinyAI (also know as Tiny AI) has been around for a few years, but with the general surge of interest in AI it is now getting more attention. There is also TinyML and Edge AI, the distinctions between which I won’t attempt to parse. The point is, AI doesn’t have to involve huge datasets run on massive servers somewhere in the cloud; it can happen on about as small a device as you care to imagine. And that’s pretty exciting.

What caught my eye was a overview in Cell by Farid Nakhle, a professor at Temple University, Japan Campus: Shrinking the Giants: Paving the Way for TinyAI.  “Transitioning from the landscape of large artificial intelligence (AI) models to the realm of edge computing, which finds its niche in pocket-sized devices, heralds a remarkable evolution in technological capabilities,” Professor Nakhle begins.

AI’s many successes, he believes, “…are demanding a leap in its capabilities, calling for a paradigm shift in the research landscape, from centralized cloud computing architectures to decentralized and edge-centric frameworks, where data can be processed on edge devices near to where they are being generated.” The demands for real time processing, reduced latency, and enhanced privacy make TinyAI attractive.

Accordingly: “This necessitates TinyAI, here defined as the compression and acceleration of existing AI models or the design of novel, small, yet effective AI architectures and the development of dedicated AI-accelerating hardware to seamlessly ensure their efficient deployment and operation on edge devices.”

Credit: Nakhle/Cell

Professor Nakhle gives an overview of those compression and acceleration techniques, as well as architecture and hardware designs, all of which I’ll leave as an exercise for the interested reader.  

If all this sounds futuristic, here are some current examples of TinyAI models:

• This summer Google launched Gemma 2 2B, a 2 billion parameter model that it claims outperforms OpenAI’s GPT 3.5 and Mistral AI’s Mixtral 8X7B. VentureBeat opined: “Gemma 2 2B’s success suggests that sophisticated training techniques, efficient architectures, and high-quality datasets can compensate for raw parameter count.”
• Also this summer OpenAI introduced GPT-4o mini, “our most cost-efficient small model.” It “supports text and vision in the API, with support for text, image, video and audio inputs and outputs coming in the future.”
• Salesforce recently introduced its xLAM-1B model, which it likes to call the “Tiny Giant.” It supposedly only has 1b parameters, yet Marc Benoff claims it outperforms modelx 7x its size and boldly says: “On-device agentic AI is here”  
• This spring Microsoft launched Phi-3 Mini, a 3.8 billion parameter model, which is small enough for a smartphone. It claims to compare well to GPT 3.5 as well as Meta’s Llama 3.
• H2O.ai offers Danube 2, a 1.8 b parameter model that Alan Simon of Hackernoon calls the most accurate of the open source, tiny LLM models.   

A few billion parameters may not sound so “tiny,” but keep in mind that other AI models may have trillions.

TinyML even has its own foundation, “a worldwide non-profit organization empowering a community of professionals, academia and policy makers focused on low power AI at the very edge of the cloud.” Its ECO Edge workshop next month will focus on “advancing sustainable machine learning at the edge,”

Rajeshwari Ganesan, Distinguished technologist at Infosys, goes so far as to assert, in AI Business, that “Tiny AI is the future of AI.”  She shares tinyML’s concern about sustainability; AI’s “associated environmental cost is worrisome. AI already has a huge carbon footprint — even larger than that of the airline industry.” With billions – that’s right, billions -- of IoT devices coming online in the next few years, she warns: “the processing power requirements may explode due to the sheer amount of data generated by them. It is imperative to shift some of the compute load to edge devices. Such small AI models can be pushed to edge IoT devices that require minimal energy and processing capacity.”

European tech company Imec is big into TinyAI, and also fears AI’s ecological impact, calling current approaches to AI “economically and ecologically unsustainable.” Instead, it believes: “The era of cloud dominance is ending: future AI environments will be decentralized. Edge and extreme edge devices will do their own processing. They will send a minimum amount of data to a central hub. And they will work – and learn – together.”

Imec sees a big future for Tiny AI in implantables. Credit: Imec

The fun part, of course, is imagining what TinyAI could be used for. Professor Nakhle says: “Among the immediate and realistic applications, healthcare stands out as a domain ripe for transformation.” He goes on to describe such potential transformations:

For instance, if paired with accessible pricing tailored to specific regions and nations, wearable devices equipped with TinyAI capabilities can revolutionize patient monitoring by analyzing vital signs and detecting anomalies in real time and promptly alerting users to irregular heart rhythms or fluctuations in blood pressure, facilitating timely intervention and improving health outcomes.

Imec sees healthcare as a particular area of focus, and offers these examples for TinyAI:

• “In genomics, improvements in data usage, algorithms and hardware lead to faster results – demonstrated in our ExaScience Lab and the Genome Analytics Platform project.
• Connected health solutions comfortably gather medical-grade data that’s used for clinical research (e.g. neurotechnology) or continuous monitoring through wearable, implantable, ingestible or non-contact technologies.
• A project such as ROBO-CURE uses artificial intelligence for personalized treatments of children with type 1 diabetes.”

Another example is one of my favorite future healthcare technologies, nanorobots. MIT just announced a tiny battery for use in cell-sized robots, which “could enable the deployment of cell-sized, autonomous robots for drug delivery within in the human body,” among other things. Now we’ll just have to get TinyAI into those robots to help achieve the many tasks we’ll be asking of them.

We’re already overflowing with great ideas for how to use AI in healthcare; we’ve barely scratched its potential.  Once we get our heads around TinyAI, we’ll find even more ways to apply it. The future is vast…and may be tiny.

Exciting times indeed.

Take My Gun, I Mean, Phone Please

I understand that states are “racing” to pass laws designed to help protect school-aged kids against something that has been a danger to their mental and physical health for a generation now, as well as adversely impacting their education. Certainly I’m talking about reasonable gun control laws, right?

Should this be banned? Credit: Bing Image Creator

Just kidding. This is America. We don’t do gun control laws, no matter how many innocent school children, or other bystanders, are massacred. No, what states are taking action on are cellphones in schools.

Florida seems to have kicked it off, with a new last year banning cell phones and other wireless devices “during instructional times.” It also prohibiting using TikTok on school grounds. Indiana, Louisiana, Ohio, and South Carolina followed suit this year, although the new laws vary in specifics.  Connecticut, Kansas, Oklahoma, Washington, and Vermont have introduced their own versions.  Delaware and Pennsylvania are giving money to schools to try lockable phone pouches.

It’s worth pointing out that school districts were not waiting around for states to act. According to a Pew Research survey earlier this year,  82% of teachers reported their district had policies regarding cellphones in classrooms. Those policies might not have been bans, but at least the districts were making efforts to control the use.

Surprisingly, high school teachers – whose students were most likely to have cellphones -- were least likely to report such policies, but, not surprisingly, the most likely to report that such policies were difficult to enforce.  Also not surprising, 72% of high school teachers say students being distracted by cellphones in the classroom is a major problem.

Russell Shaw, the head of school at Georgetown Day School in Washington, D.C., writes in The Atlantic that his parents were given free sample packs of cigarettes in school, and warns:

I believe that future generations will look back with the same incredulity at our acceptance of phones in schools. The research is clear: The dramatic rise in adolescent anxiety, depression, and suicide correlates closely with the widespread adoption of smartphones over the past 15 years. Although causation is debated, as a school head for 14 years, I know what I have seen: Unfettered phone usage at school hurts our kids. 

Similarly, last year Jonathan Haidt, a social psychologist at NYU, urged emphatically: Get Phones Out of School Now. At the least, he writes, they’re a distraction, harming their learning and their ability to focus; at worst, they weaken social connections, are used for bullying, and can lead to mental health issues. “All children deserve schools that will help them learn, cultivate deep friendships, and develop into mentally healthy young adults,” Professor Haidt believes. “All children deserve phone-free schools.”

Mr. Shaw agrees. “For too long, children all over the world have been guinea pigs in a dangerous experiment. The results are in. We need to take phones out of schools.”

Believe it or not, not everyone agrees. Some argue that, like it or not, our world is filled with cellphones, and to try to pretend that is not true will just make it harder for kids once they become adults. Along those lines, skeptics note that classrooms are filled with other devices; if kids aren’t distracted by their cellphones, there’s usually a tablet, laptop, or other device handy. And the kids can argue, hey, the adults – the teachers, the administrators, the volunteers – all have cellphones; why shouldn’t we?

Some parents are opposed to the bans. They want to know where their kids are at all times, and to be able to track them in case of an emergency. Even more chilling, some parents argue that if there is a school shooting, they want their kids to be able to call for help, and to let them know their status. None of us can forget the heartbreaking calls that some of the Uvalde children made.  

Of course, even if cellphones are banned during class time or even on school grounds entirely, those phones are going to be there once they leave the school grounds, so their potential for adverse mental impacts will still be there. If distraction is the problem – and I can see where it would be – isn’t it a similar problem for adults?  How many meetings, conferences, or social situations have you been in where many of the adults are paying more attention to their phone than to whatever is being discussed? 

I wonder if the Supreme Court has a policy about cellphones during its deliberations.

All this brings me back to guns. According to the K-12 Shooting Database, there have already been 193 school shooting incidents already this year, with 152 victims (fatal and wounded). That compares to 349 and 249 respectively in 2023, and 308/273 in 2022. I needn’t point out – but I will – that no other nation has numbers anywhere close to those.

I recently read John Woodrow Cox’s searing Children Under Fire. He points out that, even beyond the fatalities, wounded kids need not just medical care but ongoing mental health treatment. Their families usually need it too. The trauma goes well beyond the direct victims. The victim’s classmates and families often need it as well, as do schoolchildren in other districts, even in other states. Even practicing lockdowns have an impact on mental health.

He estimates that there are millions, perhaps tens of millions, of impacted schoolchildren and their families. Yet states aren’t racing to ensure support for all those victims.  

Mr. Cox suggests that the least we could do, the very least, are to ensure more background checks, to hold adults more responsible for the guns in their homes, and to conduct more research on gun violence. Instead, states are rushing to “harden” schools and to get more people with guns guarding (and teaching in) those schools. 

Oh, and to ban cellphones. We must have priorities, after all.

Look, if I was a teacher, I’d hate seeing kids on their phones during class. If I was administrator, I’d be worried about kids hanging out on their phones instead of talking with each other. If I was a parent I’d be nagging my kids to study or read a book instead of being on a screen. I get all that; I understand the drive to better manage cellphone use.

But if people think cell phones are more of a danger to their kids than gun violence, I’m going to have to disagree.   a danger to their kids than gun violence, I’m going to have to disagree.

It's in the Blood

People are fascinated by blood. Well, it would seem so, given our fondness for vampires, gory movies, and true crime stories. I’m not so keen on any of those, but I was struck by several recent developments about how blood tests can help diagnose medical problems faster, more definitively, and less invasively.

C'mon, it's not that bad. Credit: Bing Image Creator

Because, really, shouldn’t that be what our healthcare system always should strive for?

Take concussions. If you are a football fan, you’re very familiar with the problem that it seems very subjective about whether a player has suffered a concussion. They’re not the only ones. Millions of people suffer concussions each year – the vast majority of whom are not athletes – and more than half never get it evaluated.

In April Abbott received FDA approval for a rapid blood test, producing results in 15 minutes. It can be done at a patient’s beside, and not require a lab. "Clinicians have needed an objective way to assess patients with concussions," said Beth McQuiston, M.D., medical director in Abbott's diagnostics business. "When you look at all the other diseases, or other organs in the body, they all have blood tests to help assess what's happening. Now, we have a whole blood test that can help assess the brain right at the patient's bedside – expanding access to more health providers and therefore patients."

Expect to see the Abbott's i-STAT TBI cartridge and portable i-STAT^® Alinity^® instrument in emergency rooms, not to mention on NFL sidelines.

Credit: Abbott

Or Alzheimer’s disease. Many realize that it has historically been very difficult to diagnose, often not definitively until after death. Now a new study suggests a blood test can accurately diagnose it 90% of the time, which is much higher than even neurologists can do. The test is more accurate the later the stage of Alzheimer’s a person has.

Specifically, it measures “the ratio of plasma phosphorylated tau 217 (p-tau217) relative to non–p-tau217 (expressed as percentage of p-tau217) combined with the amyloid-β 42 and amyloid-β 40 plasma ratio (the amyloid probability score 2 [APS2]).” Got that?

“We’d love to have a blood test that can be used in a primary care physician’s office, functioning like a cholesterol test but for Alzheimer’s,” Dr. Maria Carrillo, chief science officer of the Alzheimer’s Association, told CNN. “The p-tau217 blood test is turning out to be the most specific for Alzheimer’s and the one with the most validity. It seems to be the front-runner.”

It’s not quite ready for use in your doctor’s office, though. “Right now, we don’t have guidelines for the use of these tests,” Dr. Eliezer Masliah, director of the division of neuroscience at the National Institute on Aging, warned NPR. Dr. Suzanne Schindler, an associate professor of neurology at Washington University School of Medicine in St. Louis, added: “Blood tests have developed incredibly fast for Alzheimer disease and I think [doctors] aren’t used to that rate of change.”

“The field is moving at a pace I never imagined 10 years ago,” Dr. Heather Whitson, a professor of medicine at Duke University, marveled to NPR.

We’re increasingly seeing FDA approved drug treatments for Alzheimer’s, so it’d be nice if we had FDA approved blood tests to more accurately use them.  

Last but not least, there’s colorectal cancer (CRC). The FDA recently approved Guardant Health’s Shield™ blood test for colorectal cancer screening, and is the first such blood test approved by the FDA as a primary screening option. A Guardant study found that it identified 87% of cancers that were at an early and curable stage, although it does less well at finding precancerous growths. The test is aimed at adults 45 and older who are at average risk.

Credit: Guardant Health

It’s not so much that it is better than colonoscopies – it’s not -- as it is that it should be easier to convince people to use. Despite the fact that CRC kills over 50,000 Americans annually, more than a third of older Americans are not getting screened. Even worse, more than three-fourths of those who die from CRC are not up-to-date with their screening.

“The persistent gap in colorectal cancer screening rates shows that the existing screening options do not appeal to millions of people,” said Daniel Chung, MD, gastroenterologist at Massachusetts General Hospital and Professor of Medicine at Harvard Medical School. “The FDA's approval of the Shield blood test marks a tremendous leap forward, offering a compelling new solution to close this gap.”

Dr. Sapna Syngal, director of strategic planning for prevention and early cancer detection at the Dana-Farber Cancer Center in Boston agrees, telling NBC News: “If this test increases the number of people getting screened, it’s going to have a huge impact.” 

The test is on the market now, and Guardant expects approval for coverage by Medicare and commercial insurance.

Most of us are used to getting routine blood tests for things like blood counts or cholesterol levels, so it’s exciting that blood tests are started to be used for other important health issues.

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Blood tests are all well and good, but they’re not (yet) the kind of test you’d routinely expect to use at home on your own. ARPA-H has even bigger aspirations. It just announced the Platform Optimizing SynBio for Early Intervention and Detection in Oncology (POSEIDON) program, the goal of which is “to develop first-in-class, at-home, synthetic Multi-Cancer-Early Detection (MCED) tests for the most sensitive and specific stage I detection of 30+ solid tumors* using only breath and/or urine samples.”

No blood draw or lab tech needed, just breath or urine samples done yourself at home. That’s something to shoot for.

“Access to a low-cost cancer screening test that does not need a lab test is so critical to preventing late-stage diagnoses, increasing survival rates, and reducing high treatment costs,” said ARPA-H Director Renee Wegrzyn, Ph.D. “With POSEIDON, we could put the power of cancer screening into homes in the U.S. and around the world.” 

“But what if any adult could, at their discretion, take an at-home test that could detect Stage I cancer? POSEIDON aims to create a future in which any adult can take a simple, over-the-counter test to screen for and detect 30+ cancers at Stage I, when they are still localized, to drastically improve the chances of curative treatment and survival,” said Ross Uhrich, DMD, MBA, ARPA-H POSEIDON’s Program Manager.

“But what if…” indeed.  ARPA-H is thinking big -- as it should. And as should we all.