Can You Say "Chemputer"?

 I learned a new word this week: “chemputer.”   It’s not a new word – it’s been around since at least 2012 -- but chances are, unless you are a chemist or maybe a synthetic biologist, it’s not a word you knew it either.   Even if you don’t care about chemistry, biology, or, for that matter, etymology, this is something you might want to pay attention to, because it may end up revolutionizing healthcare. 

The term is credited to Professor Lee Cronin of the University of Glascow.  Back in 2012, when he was first discussing the concept, he told The Guardian: “Basically, what Apple did for music, I'd like to do for the discovery and distribution of prescription drugs.”

Fast-forward most of a decade and a pandemic, and Dr. Cronin and others are closing in on that goal -- although they’ve updated their analogy to “Spotify for chemistry.”

I won’t pretend to understand either the chemistry nor the programming involved, but, simply put, chemputers automate the production of molecules – including prescription drugs, such as, for example, COVID-fighting Remdesivir.  CNBC recently profiled activity in the field, spurred by some new papers from Dr. Cronin and Dr. Nathan Collings of SRI Biosciences. 

The new paper from Dr. Cronin and his collaborators appeared in Science earlier this month, with the catchy title A universal system for digitization and automatic execution of the chemical synthesis literature.  The big breakthrough is more automation of the process, allowing robotic systems to do most of the work. 

Dr. Cronin described their work:

What we've managed to do with the development of our 'Chemical Spotify' is something similar to ripping a compact disc into an MP3.  We take information stored in a physical format, in this case a scientific paper, and pull out all the data we need to create a digital file which can be played on any system, in this case any robot chemist, including our robotic system which is an order of magnitude lower cost than any other similar robot.

The chemputer.  Credit: Lee Cronin  

Dr. Cronin’s team uses a chemical description language called XDL.  CNBC says: “XDL is to the “chemputer” as HTML is to a browser—it tells the machine what to do.”  Software called SynthReader scans descriptions of chemical processes, usually natural language processing (NPL) and translates them into XDL, when the chemputer then can actually execute in the lab.” The code can be corrected without programming knowledge and the process is hardware independent.

It’s not entirely free of human involvement – “The human will always need to be there to make sure you don’t have a dumpster on fire.” Dr. Cronin believes – but they are “dedicated to making chemical synthesis accessible to everyone, regardless of training.”

 Dr. Cronin has big ambitions:

We’re hoping that the system we’ve built will massively expand the capabilities of robot chemists and allow the creation of a huge database of molecules drawn from hundreds of years’ worth of scientific papers. 

Our system, which we're calling Chemify, can read and run XDL files which have been shared among users.  Putting that kind of knowledge directly into the hands of people with access to robot chemists could help doctors make drugs on demand in the future.   

He brags: “We’ve invented the CPU [central processing unit] for chemistry.  That’s really important right now, because all the chemistry robots in the world are not only expensive, but they can’t be programed in the same way.”

Kim Branson, the global head of artificial intelligence and machine learning at GSK, is wowed, telling CNBC: “The chemputer as a concept and the work [Cronin]’s done is really quite transformational.” 

SRI's Auto Syn.  Credit: SRI

Dr. Collins’ latest research has a similar title – Fully Automated Chemical Synthesis: Toward the Universal Synthesizer – and reports similar breakthroughs.  Their synthesizer AutoSyn “makes milligram-to-gram-scale amounts of virtually any drug-like small molecule in a matter of hours.”  Their paper demonstrated synthesis of ten known drugs and predicts success for a high percent of many other FDA approved small molecule drugs. 

Dr. Collins is a big believer in the combination of AI and automation to improve the pharma R&D process.  He wrote earlier this year: “Progress in AI offers the exciting possibility of pairing it with cutting-edge lab automation, essentially automating the entire R&D process from molecular design to synthesis and testing – greatly expediting the drug development process.”

“The majority of chemistry hasn’t changed from the way we’ve been doing it for the last 200 years. It’s very manual, artisan driven process,” Dr. Collins told CNBC.  “There’s billions of dollars of opportunity there.”  No wonder Dr. Branson and other pharma executives are paying close attention.

Darpa is also paying close attention.  SRI International, the parent of Dr. Collins’ Bioscience division, just received $4.3 from Darpa for a tool to help automate production of therapeutics for pandemics and other biological threats.  

Darpa also is funding a Make-It program to automate “small molecule discovery and synthesis to propel the field beyond conventional batch-based, intuition-driven capabilities,” and a related Accelerated Molecular Discovery program, in which, as Anne Fisher, the program manager, told CNBC: “We’re now trying now to harness what we’ve done in Make-It and expand it out so we can teach computers how to discover new molecules.”

Credit; SRI

Think about that “Teach computers how to discover new molecules” and let that sink in.  As Dr. Collins says, “This is still a very new science.  It’s started to explode really in the last 18 months.”

All this is taking place as 3D printing for pharmaceuticals is also starting to take off, such as for “low-cost production of customized pill medications for patients who need special dosing, quantities or composition of drugs. Pills can be 3D printed in unique sizes, shapes and with slow-release capabilities.”  The FDA is still working on how to regulate 3D printing of medical products (which now include prostheses, orthopedic and other implants, pharmaceuticals, and even organs). 

It better start thinking about chemputers, or at least the products made by them. 

At the very least, we can expect that chemputers and 3D printing could greatly speed and democratize the production of pharmaceuticals.  Imagine your doctor or pharmacist producing your medicine on the spot – or perhaps doing it yourself, in your own home.  Further development of AI could also greatly speed up on the discovery process, which could have major implications not just for our health but also for the pharmaceutical industry.  The old models are up for grabs. 

So, get to know chemputers.  They may be in your future.    

Not Just Faxes

I missed it when it was first announced in Japan, but fortunately the U.S. mainstream media has finally picked up on the story, with articles in both The Washington Post and The Wall Street Journal: Japan’s new Administrative Reform Minister Taro Kono has “declared war” on fax machines, among other paper-based traditions.  

Wait, what?  “Administrative Reform Minister?”  The U.S., or at least the U.S. healthcare system, has to hear about this. 

Mr. Kono is a well known Japanese politician, including stints as Defense Minister and Foreign Minister.  He is thought of as something of a maverick, at least by Japanese political standards.  New Prime Minister Suga installed Mr. Kono in mid-September, making overhaul of bureaucracy a top priority: “Wherever there are problems, I want all of them brought to Mr. Kono for handling on behalf of the nation.” 

Mr. Kono set up a hotline for people to report government red tape, which was quickly overwhelmed with thousands of examples.  It soon reopened.

It didn’t take long for Mr. Kono to start calling for significant changes.  “To be honest, I don’t think there are many administrative procedures that actually need printing out paper and faxing,” he said in a press conference in late September.  “My job is to clear the road of obstructions to allow the Ferraris and Porsches of digital innovation to speed through.”

I wonder what Honda and Toyota thought about that.

Part of the problem in Japan is the hanko, a personal stamp that is routinely used for authentication (and which thus requires paper.)  He’s now at war with that as well, tweeting:

We checked 800 most often used government procedures with hanko, or name stamp or seal, and found few of them need to continue with hanko. This is the first step to make those procedures online.

One ally, futurist Morinosuke Kawaguchi, pointed out:

More than 97 per cent of the documents that are produced in companies and government offices presently need a hanko, but these are hanko that can be purchased in a convenience store, so there is no meaning to this habit.  It makes no sense, it’s completely ridiculous.

If you’ve ever envied Japan for its bullet trains, its early adoption of robots, or its broad use of consumer electronics, you may be surprised to hear that more than 95% of Japanese businesses still use faxes, and 34% of Japanese households have a fax.  Mr. Kawaguchi admitted: “It may be 1970s technology, but it is extremely secure and very difficult for someone on the outside to hack…Digitisation may make things more efficient, but there is clearly a trade-off when it comes to security.”

Jonathan Coopersmith, a Texas A&M professor who is an expert on faxes, told WaPo: 

The primary mode of writing is by hand, and this is a technology that fits this perfectly.  One of the reasons it’s still there is that you have an older generation that’s never really wanted to use computers, and a lot of small businesses that never adopted computers and didn’t need to.

Not surprisingly, the COVID-19 pandemic has been a big driver in the anti-fax initiative.  Health care professionals were overwhelmed by the amount of reports that had to be prepared by hand and then faxed.  “Come on, let’s stop this already,” one physician tweeted.  “Even with corona, we’re handwriting and faxing.”  Mr. Kono quickly retweeted it, even though he was still in his former position as Defense Minister – and within a week the health ministry announced a system of online filing (which, not surprisingly, has not entirely succeeded).

An independent report on Japan’s response to the pandemic found that their system “made it difficult to grasp the spread of infection in real time nationwide, and exhausted health center staff.  The new coronavirus crisis was also Japan’s ‘digital defeat.’”

We don’t have hankos in the U.S., and we’re not as reliant on faxes as Japan is, even in our healthcare system.  But red tape, inefficiencies, and antiquated technology?  Yeah, we’ve got all that, especially in healthcare.  But where’s our Secretary of Administrative Reform?  Where are our Chief Administrative Reform Officers? 

Heck, where are our hotlines to report red tape? 

Even now, well over six months into our pandemic response, we have a slapdash, state-by-state (or even county-by-county) system of reporting, with hospitals and HHS still struggling to figure out what and how to report.  We’re driving by looking in our rearview mirror, and images – data -- may be distorted.  They certainly aren’t real-time.  Dr. Ashish Jha, director of Harvard’s Global Health Institute, lamented: “The CDC during this entire pandemic has been two steps behind the disease,”

“We are woefully behind,” one senior CDC official said.  She likened the state of U.S. public health technology to “puttering along the data superhighway in our Model T Ford.”  Where are those Ferraris and Porsches Mr. Kono is expecting? 

And, to be fair, it’s not just the U.S.  Jen Spahn, Germany’s federal minister of health, admitted:

Faxes are still the most used way of communication in our health system, at least when it comes to communicating between the different players. Within a hospital, that might be very much digitised, but as soon as you want to communicate with another hospital or another player in the healthcare system, it’s very much like the 1990s and not like 2020.

Yoshimitsu Kobayashi, chairman of Mitsubishi Chemical Holdings, sees the pandemic as an opportunity: “The very negative damage it has inflicted on Japan has in turn served as a powerful accelerator.  If we miss this chance, we won’t be able to do it next time.”

Economist Paul Romer is usually credited with the quote, “A crisis is a terrible thing to waste.”  Well, we certainly have a crisis, and I’m worried we’re going to waste it.  Using it to just get rid of faxes would be a waste.  We’re already using it to streamline development of therapeutics and vaccines, although not without problems.  But will we use it to solve fundamental problems in our healthcare system, such as inequities, inefficiencies, and infrastructure? 

Maybe we could recruit Mr. Kono to do the job. 

A War on Science Is a War on Us

 We’re in the midst of a major U.S. election, as well as hearings on a Supreme Court vacancy, so people are thinking about litmus tests and single issue voters – the most typical of which is whether someone is “pro-life” or “pro-choice.”  Well, I’m a single issue person too; my litmus test is whether someone believes in evolution. 

I’m pro-science, and these are scary times.

Within the last week there have been editorials in Scientific American, The New England Journal of Medicine, and Nature – all respected, normally nonpartisan, scientific publications – taking the current Administration to task for its coronavirus response.   Each, in its own way, accuses the Administration of letting politics, not science, drive its response. 

SA urges voters to “think about voting to protect science instead of destroying it.”  They cite, among other examples, Columbia Law School’s Silencing Science Tracker, which “tracks government attempts to restrict or prohibit scientific research, education or discussion, or the publication or use of scientific information, since the November 2016 election.”  Their count is over 450 by now, across a broad range of topics in numerous federal agencies on a variety of topics.   

The SA authors declare:

Science, built on facts and evidence-based analysis, is fundamental to a safe and fair America. Upholding science is not a Democratic or Republican issue.

Similarly, NEJM fears:

Our current leaders have undercut trust in science and in government, causing damage that will certainly outlast them. Instead of relying on expertise, the administration has turned to uninformed “opinion leaders” and charlatans who obscure the truth and facilitate the promulgation of outright lies.

Jeff Tollefson, in Nature, warns:

As he seeks re-election on 3 November, Trump’s actions in the face of COVID-19 are just one example of the damage he has inflicted on science and its institutions over the past four years, with repercussions for lives and livelihoods. 

“This is not just ineptitude, it’s sabotage,” Jeffrey Shaman, an epidemiologist at Columbia University, told Mr. Tollefson about the Administration’s pandemic efforts.  “He has sabotaged efforts to keep people safe.”  Christine Todd Whitman, former New Jersey Governor and EPA head, added: “I’ve never seen such an orchestrated war on the environment or science.”

The Administration likes to tout the admittedly remarkable progress that pharmaceutical companies have made in therapeutics and vaccines – Operation Warp Speed! -- but the constant battles with both the FDA and the CDC (EUAs for everything!) have left the American public skeptical of supposed breakthroughs.  In the wake of President Trump’s recent embrace of monoclonal antibodies, The Washington Post lamented:

This has been the 2020 pattern: Politics has thoroughly contaminated the scientific process. The result has been an epidemic of distrust, which further undermines the nation’s already chaotic and ineffective response to the coronavirus.

 A Pew Research survey found Americans evenly split between those who would definitely/probably get a vaccine as soon as it was available and those who would not – and the percent willing has dropped from 72% in May.  Almost 80% fear the approval process will move too fast; in other words, that the science will be trumped by political concerns. 

“Warp speed really isn’t something I want from my medications, especially not ones for my children,” one physician told Alexandra Feathers in Slate.

A separate survey, from Axios/Ipsos, found that only 8% of Americans now have a “great deal” of faith in the FDA to look out for their best interests; only slightly more than half even had a fair amount of faith.  Trust in the CDC has also fallen. 

Science is losing. 

As tempting as it is to blame the current Administration for this war on science, it is a symptom of the problem, not the cause.  Some examples:

• One in four Americans believe the sun rotates around the earth. 
• Depending on how the question is asked, between a fifth and a third of Americans don’t believe in evolution at all, with another third believing in evolution “directed” by God. 
• Only three-fourths are Americans believe climate change is happening, with smaller percentages believing any such change is due to human actions. 
• Anti-vaccination beliefs had been growing steadily even prior to COVID, for well-understood, highly effective vaccines.    
• American school children continue to rank mediocre in science and math; adult Americans get a gentleman’s “D” for their science knowledge. 
• Only 73% of Americans think science has, on balance, had a positive impact on society; only 35% have a “great deal” of confidence in scientists to act in the public interest (although 51% had “fair” confidence). 

Politicians can get away with downplaying science because we let them; we let them because some of us don’t know enough, and others among us don’t care enough.  Anti-vaxxers were initially seen as an aberration, too small to worry about, but became a problem.  Now people not getting a COVID vaccine could be the difference between months of pandemic and years of pandemic.

Cultural wars have become wars on science.  Experts agree that wearing a mask and social distancing are the keys to our battle against COVID for the next many months, yet to many wearing a mask is a “personal choice” -- even when not wearing one is a risk not just for the person not wearing one but to them people around them. 

We should listen to the science.

It’s easy to get caught up in partisan politics about all this, but that’s wrong.  Science doesn’t care about your politics.  COVID doesn’t ask who you’re going to vote for.  Climate change doesn’t stop if you refuse to believe in it.  As writer Valorie Clark tweeted:

Stop asking candidates if they “believe in” climate change and start asking if they understand it. It’s science, not Santa Claus.

We should stop allowing candidates to tell us there’s a metaphorical Santa Claus and start demanding fact-based decisions. We should stop thinking science is something only scientists care about and start accepting that our lives depend on science, so we better understand how. 

Many might claim they are bad at science, but I think about what mathematician Paul Lockhart wrote many years ago in A Mathematician’s Lament.  If music was taught like math (or science) is, few would enjoy listening to it and even fewer would play it. It’s incumbent on scientists and educators to make science more accessible and understandable for the rest of us. 

We’ve failed the science test so far when it comes to COVID, and it has literally cost us hundreds of thousands of lives.  It’s not the first such test we’ve failed, but we can, should, and must do better – starting now. 

Attention, Walmart Patients

When Walmart announced earlier this summer that it was opening an insurance agency to sell Medicare-related products and services plans, I thought, “that’s it?”  When Walmart announced later in the summer that it was partnering (first with Microsoft, then with Oracle) in the bid to buy TikTok, I thought, “well, isn’t that interesting?”  And when Walmart announced a few days ago that it was partnering with Clover Health to offer Medicare Advantage plans, I thought: “it’s about time.”

You know Walmart.  265 million people (worldwide) shop at its stores each week.  Ninety percent of Americans live within 10 miles of a Walmart store.  It is estimated that 95% of Americans shop at Walmart during the year.  In over 200 U.S. markets, it accounts for at least 50% of grocery sales.  It is the fifth largest pharmacy chain by revenue. 

And Walmart has been shaking up healthcare for some time.  Way back in 2006, it introduced its $4 Prescriptions program that upended pharmacy pricing.  In 2008, it started offering in-store retail clinics, initially in partnership with hospitals and now operates on its own. 

Last year it started offering standalone clinics – Walmart Health – that went far beyond typical retail clinics.  They feature primary care, dental, lab and imaging, plus vision and audiology, and are starting to rapidly expand their footprint, aiming for 22 locations, in multiple states, by the end of 2021.  Patients can go online to view prices of services and book appointments. 

Then-President of Walmart U.S. Health and Wellness Sean Slovenski declared, “We're bringing people into the health care system that have not traditionally been in it and identifying their needs.  We're kind of creating an entire new market of customers."  Commenting on the clinic’s low-cost, disclosed-in-advance prices and all-in-one services, Mr. Slovenski said: “We didn’t set out to disrupt healthcare. We set out to meet the needs of our customers at Walmart.”

To help its customers use technology in their health care journey, earlier this year it acquired technology from CareZone that “helps individuals and families manage medicine and chronic illness for each member of the household.”  They can also scan insurance cards or prescription drug labels. 

Walmart is beefing up its clinics by a new deal with Oak Street Health.  Marcus Osborne, Senior Vice President, Walmart Health said: “As we grow Walmart Health locations in other markets, we think Oak Street Health’s innovative value-based healthcare model will help us continue to deliver on our live better promise at these locations.”

Not to be outdone, Walmart subsidiary Sam’s Club just announced it is going nationwide on a collaboration with telehealth provider 98point6 that it piloted in September 2019.  It offers a subscription service that features unlimited $1 telehealth visits.  “Offering access to telemedicine was on our roadmap in the pre-COVID world, but the current environment expedited the need for this service to be easily accessible, readily available and most of all, affordable,” said John McDowell, Vice President, Pharmacy Operations and Divisional Merchandise, Sam’s Club. 

Walmart hasn’t been content to just offer health care services; it has been active on the payor front too.  In 2010, it partnered with Humana to offer a Medicare Part D plan, which it still offers.  For its own employee health program, it has had a Centers of Excellent program for over twenty years, and has tested ACOs, bundled payments, and value-based purchasing.  A couple years ago there was much discussion about a Walmart-Humana merger/acquisition, which did not pan out – yet. 

Which brings us to the Clover Health partnership, called LiveHealthy.  Clover Health President & CTO Andrew Toy said:

The Walmart brand is synonymous with the best value and low prices, and that's exactly what we're doing at Clover.  By offering affordable insurance plans with an open network  of doctors and hospitals, we are democratizing high-quality care and bringing it to individuals and communities that have previously been overlooked by other insurers.

LiveHealthy will start out in eight Georgia counties, with a network of 31 hospitals and 8,000 clinicians – including Walmart Health locations.  The plan is being billed as “Clover-powered,” but follows the Walmart value approach – zero premium, “free” primary care visits, lab tests, and preventive dental services, not to mention $100 every quarter to spend on OTC items at Walmart. 

In the scheme of things, Clover Health has a small membership/footprint.  Its main strength is its technology, specifically Clover Assistant that “gives your primary care doctor a complete view of your overall health and sends them care recommendations that are personalized for you, right when you're in the appointment,” using “data, clinical guidelines, and machine learning to surface the most urgent patient needs.”

I’ve always wondered why Walmart hadn’t pursued partnerships with/acquisitions of managed Medicaid plans, such as Centene or Molina Healthcare (both of which are actively pursing their own acquisitions).   Clover Health’s website says: “Clover proudly serves many low-income and often overlooked communities, which is core to the company’s mission of bringing healthcare to people who are most in need and commonly ignored by other insurers.”  That dovetails quite nicely with serving a Medicaid or dual eligible (Medicare and Medicaid) population. 

Lest anyone think Walmart is solely focused on healthcare, there is:

• The aforementioned interest in TikTok, which Walmart believes “will provide Walmart with an important way for us to expand our reach and serve omnichannel customers as well as grow our third-party marketplace, fulfillment and advertising businesses.”  It would especially boost Walmart’s presence for younger audiences.
• The introduction of Walmart+, it’s answer to Amazon Prime that some analysts think could lead to 10 million subscribers by the end of 2021.  It includes unlimited free delivery on more than 160,000 items.
•  Its surging online sales, which have nearly doubled in the last quarter, especially for online groceries.  “You see Amazon following behind Walmart on this,” Edward Yruma, a retail analyst at KeyBanc Capital Markets, told The New York Times.

 Walmart U.S. CEO John Furman believes: “The demand definitely tells us that Americans are looking for access to quality care, and we think Walmart — its footprint — should be a part of that.”  Maybe “Walmart” doesn’t carry the same cache as, say, “The Mayo Clinic” when it comes to healthcare, but its brand for value and convenience is hard to match, and that may be enough to make it a force in healthcare. 

Pundits spend a lot of time wondering what Amazon will do in healthcare, when.  It is, indeed, taking some interesting steps, but no one should be overlooking what Walmart is doing. 

Or soon will be.