A corrected history of mRNA vaccines

According to the world’s most prestigious scientific journal, here’s how the history of mRNA vaccines begins:

In late 1987, Robert Malone performed a landmark experiment. He mixed strands of messenger RNA with droplets of fat, to create a kind of molecular stew. Human cells bathed in this genetic gumbo absorbed the mRNA, and began producing proteins from it.

Realizing that this discovery might have far-reaching potential in medicine, Malone, a graduate student at the Salk Institute for Biological Studies in La Jolla, California, later jotted down some notes, which he signed and dated. If cells could create proteins from mRNA delivered into them, he wrote on 11 January 1988, it might be possible to “treat RNA as a drug”. Another member of the Salk lab signed the notes, too, for posterity. Later that year, Malone’s experiments showed that frog embryos absorbed such mRNA. It was the first time anyone had used fatty droplets to ease mRNA’s passage into a living organism.

Those experiments were a stepping stone towards two of the most important and profitable vaccines in history: the mRNA-based COVID-19 vaccines given to hundreds of millions of people around the world. Global sales of these are expected to top US$50 billion in 2021 alone.

The above Nature article is dated September 14, 2021. In late December 2021/early January 2022, the above-referenced Robert Malone was censored by YouTube (UK Independent) and unpersoned by Twitter (Daily Mail). A mixture from the two sources:

Given the doctor’s contested views on Covid-19, including his opposition to vaccine mandates for minors, the act by YouTube has sparked several accusations of censorship amongst right-wing politicians and political commentators.

Malone even questioned the effectiveness of Pfizer’s Covid-19 vaccine in a tweet posted the day before his account was suspended on December 30

He told Rogan that government-imposed vaccine mandates are destroying the medical field ‘for financial incentives (and) political a**-covering’

Malone responded by questioning: ‘If it’s not okay for me to be a part of the conversation even though I’m pointing out scientific facts that may be inconvenient, then who is?’

(What did Malone do for work between 1987 and now? According to Wikipedia, he graduated medical school in 1991, was a postdoc at Harvard Medical School (yay!), and then worked in biotech, including on vaccine projects. “Until 2020, Malone was chief medical officer at Alchem Laboratories, a Florida pharmaceutical company,” suggests that he might live here in the Florida Free State.)

How long would we have to wait for a corrected history of mRNA vaccines from which the unpersoned Malone would be absent? January 15, 2022, “Halting Progress and Happy Accidents: How mRNA Vaccines Were Made” (New York Times), a 30-screen story on my desktop PC. The Times history starts in medias res, but if we scroll down to the point in time where Nature credits Malone, both Malone and Salk are missing:

The vaccines were possible only because of efforts in three areas. The first began more than 60 years ago with the discovery of mRNA, the genetic molecule that helps cells make proteins. A few decades later, two scientists in Pennsylvania decided to pursue what seemed like a pipe dream: using the molecule to command cells to make tiny pieces of viruses that would strengthen the immune system.

The second effort took place in the private sector, as biotechnology companies in Canada in the budding field of gene therapy — the modification or repair of genes to treat diseases — searched for a way to protect fragile genetic molecules so they could be safely delivered to human cells.

The third crucial line of inquiry began in the 1990s, when the U.S. government embarked on a multibillion-dollar quest to find a vaccine to prevent AIDS. That effort funded a group of scientists who tried to target the all-important “spikes” on H.I.V. viruses that allow them to invade cells. The work has not resulted in a successful H.I.V. vaccine. But some of these researchers, including Dr. Graham, veered from the mission and eventually unlocked secrets that allowed the spikes on coronaviruses to be mapped instead.

Perhaps the Times just didn’t have enough space in 30 screens of text to identify Malone? The journalists and editors found space to write about someone who wasn’t involved in any way:

“It was all in place — I saw it with my own eyes,” said Dr. Elizabeth Halloran, an infectious disease biostatistician at the Fred Hutchinson Cancer Research Center in Seattle who has done vaccine research for over 30 years but was not part of the effort to develop mRNA vaccines. “It was kind of miraculous.”

There was plenty of space for a photo of an innumerate 79-year-old trying to catch up on six decades of biology. The caption:

From left: Dr. Graham, President Biden, Dr. Francis Collins and Kizzmekia Corbett. The scientists were explaining the role of spike proteins to Mr. Biden during a visit to the Viral Pathogenesis Laboratory at the N.I.H. last year.

For folks in Maskachusetts who’ve had three shots and are in bed hosting an Omicron festival, the article closes with an inspiring statistic:

He was in his home office on the afternoon of Nov. 8 when he got a call about the results of the study: 95 percent efficacy, far better than anyone had dared to hope.

See also the NYT for Massachusetts hospitalization stats in a population that is 95 percent vaccinated with a 95 percent effective vaccine:

So… it was two weeks from Robert Malone being unpersoned by the Silicon Valley arbiters of what constitutes dangerous misinformation to an authoritative history in which Malone is not mentioned.

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Is “data scientist” the new “programmer”?

Back in the 1970s, being a “programmer” meant writing one or files of code that input data, processed it in some way, and then output a result. A program that occupied more than 256 KB of memory, even on a mainframe, would have been considered bloated (and wouldn’t have run at all on a “minicomputer,” at least not without a painful process of overlaying). Thus, there tended to be a lot of interesting stuff going on within every few lines of code and certainly an entire file of code might contain nearly everything interesting about an application.

Today’s “software developer” is typically mired in tedium. To trace out the code behind a simple function might require going through 25 files, each of which contains a Java method that kicks a message to another method in some other file. Development tools such as Eclipse can speed up the tedious process of looking at a 20-layer call stack, but there remains a low density of interesting stuff to look at. A line of code that actually does something is buried amidst hundreds of lines of glue, interface, and overhead code. How did applications get so bloated and therefore boring to look at? I blame hardware engineers! They delivered the gift of infinite memory to the world’s coders and said coders responded with bloat beyond anyone’s wildest imagination.

Does the interesting 1970s “programmer” job still exist? While teaching an intro “data science” class at Harvard, I wondered if the person we call a “data scientist” is doing essentially the same type of work as a 1970s Fortran programmer. Consider that the “data scientist” uses compact languages such as SQL and R. An entire interesting application may fit in one file. There is an input, some processing, and an output answer.

Readers: What do you think? Is it more interesting to work in “data science” than “software engineering” or “programming”?

Older readers: Is today’s “data science” more like a programming job from the 1970s “scarce memory” days?



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Fallout from the Java = SUV posting

The “Java = SUV posting” continues to resonate in my inbox.

The last two students using Java dropped 6.171.  They were not keeping pace with the PHPers and those who sold their souls to Bill Gates.  (Recall that all the students in 6.171 had built a 10,000-line Java program in 6.170 so they all knew the language itself quite well.)

Lots of professional Java programmers emailed to say “If only those students had used Libraries X and Y, they would have done okay.”  Sadly X and Y were never the same in any two emails so it is easy to understand how the students went wrong (i.e., it is not obvious how one is supposed to choose among the 100 different ways to get something done in the world of Java tools).

Similarly there was no agreement among Java programmers as to whether it is good to have SQL queries prominently featured in source code or better to make everything into Java objects and magically generate SQL behind the programmers’ backs.  Half of those emailing said that SQL was impossibly hard to write and what people really needed was to see the programmers’ custom-created methods.  The other half seemed to think that a database application ought to be primarily expressed in SQL, a concise declarative query language that has been standard for 25+ years.  These are 100% incompatible points of view.

My friend Curtis, an old-time Silicon Valley monster C hacker, AIMed me to say that he’d seen the Slashdot article:

“My problem with Java is that it makes hard things hard, and easy things hard.  The amount of hassle doesn’t scale with the complexity of the problem.  Whereas with PHP you can write “Hello World” without having to read a 200-page book.  Java is a train wreck with dozens of classes with slightly different methods that do similar things.  On the other hand, it kills me that the PHP database interface is so bad.  Actually PHP just kills me anyway…why they had to invent a new language, I’ll never know.”

I pointed out to Curtis that the latest Technology Review, MIT’s alumni rag, picked the developer of PHP as one of its “100 Bold Young Innovators You Need to Know”:

“Rasmus Lerdorf has learned five languages while living around the world.  But it’s the language he invented that has had global impact.  In 1995, without any formal programming training, Lerdorf developed a server language to help him set up Web sites. … He named the language PHP, for PHP hypertext preprocessor.”

Curtis’s response to Tech Review?  “People mistake creation for innovation”.

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Java is the SUV of programming tools

Our students this semester in 6.171, Software Engineering for Internet Applications have divided themselves into roughly three groups.  One third has chosen to use Microsoft .NET, building pages in C#/ASP.NET connecting to SQL Server.  One third has chosen to use scripting languages such as PHP connecting to PostgreSQL and sometimes Oracle.  The final third, which seems to be struggling the most, is using Java Server Pages (JSP) with Oracle on Linux.  JSP is fantastically simpler than “full-blown J2EE”, which is the recommended-by-Sun way of building applications, but still it seems to be too complex for seniors and graduate students in the MIT computer science program, despite the fact that they all had at least one semester of Java experience in 6.170.

After researching how to do bind variables in Java (see the very end of http://philip.greenspun.com/internet-application-workbook/software-structure), which turns out to be much harder and more error-prone than in 20-year-old C interfaces to relational databases, I had an epiphany:  Java is the SUV of programming tools.

A project done in Java will cost 5 times as much, take twice as long, and be harder to maintain than a project done in a scripting language such as PHP or Perl.  People who are serious about getting the job done on time and under budget will use tools such as Visual Basic (controlled all the machines that decoded the human genome).  But the programmers and managers using Java will feel good about themselves because they are using a tool that, in theory, has a lot of power for handling problems of tremendous complexity.  Just like the suburbanite who drives his SUV to the 7-11 on a paved road but feels good because in theory he could climb a 45-degree dirt slope.  If a programmer is attacking a truly difficult problem he or she will generally have to use a language with systems programming and dynamic type extension capability, such as Lisp.  This corresponds to the situation in which my friend, the proud owner of an original-style Hummer, got stuck in the sand on his first off-road excursion; an SUV can’t handle a true off-road adventure for which a tracked vehicle is required.

With Web applications, nearly all of the engineering happens in the SQL database and the interaction design, which is embedded in the page flow links.  None of the extra power of Java is useful when the source of persistence is a relational database management system such as Oracle or SQL Server.  Mostly what you get with Java are reams of repetitive declarations at the top of every script so that the relevant code for serving a page is buried several screens down.  With a dynamic language such as Lisp, PHP, Perl, Python, Tcl, you could do bind variables by having the database interface look at local variables in the caller’s environment.  With Java the programmer is counting question marks in the SQL query and saying “Associate the 7th question mark with the number 4247”, an action that will introduce a bug into the program as soon as the SQL query is modified (since now the 7th question mark has been moved to become the 8th question mark in the query).

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