Coffee Break: Biotech vs. Science, NIH Under New Management, More on Malaria, Dreams of De-Extinction, and an Aside on the State of America

Part the First: Is This How to Do Science? San Diego, with the University of California-San Diego and the Scripps Research Institute leading the way, has been a Biotech/Little Pharma hotspot since the beginning, a strong third behind Boston and the Bay Area. Ups and downs are common, but in the current climate it is not clear that recovery is in the offing. From STAT, Uncertainty clouds the San Diego biotech hub, with jobs and capital scarce:

Ever since Vince Kato was laid off, he has felt like he was just two to three months away from landing a new position. But more than a year later, he’s running out of options, and out of time. Kato, who was a senior engineer at Illumina, was let go in March 2024 and since then, has applied without success for hundreds of positions at biotech startups and larger pharma firms, including roles he is overqualified for. With a monthly rent of $3,600 eating through his savings, he’s now facing hard choices.

“I’ve either got to leave San Diego, move back to Minnesota, or something. I don’t know,” Kato said. “At this point, I’m just reaching the end of my rope financially.”

Rather than discuss the outlook for biomedical science in general and Vince Kato in particular, the concerns expressed here are rather different. Not to mention shortsighted:

(Local analysts) remain convinced the local industry is spring-loaded for growth once investment dollars start flowing more freely and the industry’s IPO slump ends. Josh Schimmer, a market analyst for financial services firm Cantor Fitzgerald, finds reason for optimism in recent data. In a note to investors at the end of last year, Schimmer pulled data on how the stocks of dozens of San Diego’s publicly traded biotechs performed in 2024. He found that local companies’ shares increased by 29% at the median during a year in which the XBI, a closely tracked index of biotech stocks, was flat…“We continue to see very differentiated, very powerful companies, technologies, products, platforms, emerging out of San Diego.”

That’s what Hallie Kuhn sees, too. Kuhn, life sciences lead for Alexandria Real Estate, noted that, since 2023, for every dollar of venture capital poured into local biotech companies, there have been $5.85 in returns from mergers and acquisitions, according to data Alexandria has pulled from Pitchbook and market intelligence firm Evaluate. That exceeded the returns on investment for biotechs in Boston and San Francisco, where acquisition-to-investment ratios during this period were 3.33 and 0.76, respectively.

“From a venture perspective, our dollars here go really far,” she said.

And so it goes. In typical American fashion, very little about the science while the focus stays on money – which is what matters as Big Pharma buys up Little Pharma and provides a windfall for VC and PE while the “principals” of Little Pharma cash out with a unicorn and go sailing. To wit:

Three of the larger biotech deals in the past couple years were from Novartis, which bought gene therapy startup Kate Therapeutics, siRNA company DTx Pharma, and kidney-focused biotech Regulus Therapeutics. Those deals helped convince the Swiss pharma giant to expand its existing investment in the region. In April, Novartis announced plans to establish a $1.1 billion research hub in San Diego, its second such facility in the United States.

“We keep finding really good biotech companies there,” she said. “We really like the … dense packing together of pharma and biotech. It means people mix together, there are shared facilities. We generally find that’s the sort of environment that stimulates innovation.”

Behold, the Bayh-Dole Act of 1980 doing what it does best! Science in the United States has strayed so far from the post-war vision of Vannevar Bush that it may never recover. Especially if the Current Administration succeeds in its goal to Make American Science Great Again (MASGA) by returning it to a Gold Standard Science™ that admits of no uncertainty or leaves no room for the unexpected, and ignores the rest of the world. When Max Delbrück counseled his students and colleagues to always leave room for the unexpected result in their experiments, he was talking about all of science, not just what they were doing in their individual laboratories. As an aside, the first true discovery I made as a newly independent scientist happened because I left room for the unexpected in an experiment and found an accidental mutant that was the key to a function of my favorite protein.

Well, MASGA will require a return to what was a golden age of American science when scientists in independent research institutions, universities and colleges, medical schools, along with intramural researchers at the National Institutes of Health, are given the support to “interrogate” the living world in search of new and useful knowledge, with few preconditions. This is how to do science, if you want it to be productive. There is no other way.

Part the Second: The Strange Case of the Current Director of the National Institutes of Health. Jay Bhattacharya, MD-PhD (Stanford) is often referred to as a physician in the popular press. Although he has an MD, he is not a physician (neither is Casey Means, MD, who is apparently still the Surgeon General designee despite not having a license to practice medicine after she left her ENT residency without finishing it). Bhattacharya went straight from his medical school graduation to the PhD program in Economics at Stanford. He never did a residency and thus has never practiced medicine. In most jurisdictions it would be illegal for him to imply he is a “doctor,” if that is taken to have the same meaning as “physician.” Nor has he ever done any biomedical research as far as I can tell in a quick search of PubMed (NB: I may well have missed it; PubMed is indispensable but not infallible).

He has, on the other hand, received NIH support for published research on the economics and delivery of healthcare in the United States. This is covered here: Jay Bhattacharya once studied health disparities. As NIH director, he’s allowed such research to wither:

The April announcement of National Institutes of Health director Jay Bhattacharya’s appointment and his public profile at Stanford University, where he was a professor of health policy, both state that his work has focused on vulnerable populations, and he’s published at least five papers on racial health disparities. In June, he specifically lauded sickle cell research as an NIH success, highlighting it as the kind of work “that advances the health and well-being of minority populations,” and that the NIH should continue supporting. “It absolutely must,” he told podcaster Andrew Huberman.

Yet that same month, Duke University hematologist Charity Oyedeji was notified that her $750,000 NIH grant was terminated. She’d been studying how to assess and stave off disability for Americans with sickle cell disease, who tend to age prematurely, and most of whom are Black. The June 16 notice said that “such diversity, equity, and inclusion (“DEI”) studies are often used to support unlawful discrimination on the basis of race … which harms the health of Americans.”

To Oyedeji, that made it sound like her patients weren’t worth spending research time or money on. “People in this project are Americans,” she told STAT. “So do you not think that diverse populations are considered in this blanket of ‘Americans?’ Is ‘Americans’ the white people?”

Why is it that most patients in the US with sickle cell disease are Black? It has absolutely nothing to do with their race, which aside from superficial inherited characters is a sociopolitical construct convenient for eugenicists and their political minions. The malaria parasite does not grow well in the red blood cells of carriers of the sickle cell trait [one gene for Hemoglobin S (HbS) instead of two]. Thus, carriers are resistant to malaria and have mild symptoms of sickle cell disease only under extreme conditions (e.g., sustained exertion, high altitude). People with ancestors from sub-Saharan Africa are not the only populations that are prone to sickle cell disease. Those from Southeast Asia and the Mediterranean basin are also at risk for sickle cell disease, where malaria remains endemic. By the way, as the climate warms, malaria is probably returning the North America, too, as it was for my father as a child in southern Louisiana ninety years ago.

Whatever the justification for termination of a grant to study the trajectory of sickle cell disease, it cannot be DEI. Nevertheless:

Despite his avowed support for vulnerable people, Bhattacharya’s tenure has seen such science swept up in the Trump administration’s attack on DEI. Grants for health disparities research have been terminated left and right, sometimes affecting the very topics he’s said are worth studying. When confronted, he claimed, incorrectly, that such cuts hadn’t happened. Whether he’s been unwilling or unable to prevent them — or simply unaware of what’s happening within his own agency — is hard to say.

Or maybe it is not really hard to say. Maya Angelou famously and correctly said, “When someone shows you who they are, believe them the first time.” Jay Bhattacharya is one of three authors of the Great Barrington Declaration, which was the “let ‘er rip” manifesto for dealing with COVID-19 by letting the virus run wild to elicit herd immunity that would protect the vast majority from the pandemic. Never mind that a virus that does not elicit durable immunity, either through infection or vaccination, will not be controlled by herd immunity (unlike measles). This document is still cited by those inclined to believe what is emitted from one of our primary Merchants of Doubt, the American Institute for Economic Research. One may fairly conclude that Jay Bhattacharya, MD-PhD, is a libertarian for whom health is a personal, not a public matter. In this he is no different from the general run of such people. Those of us who get sick, get what we deserve. So saith the current Secretary of Health and Human Services. Like other things, directives flow downhill with a will of their own. And unlike every other Director of NIH, Jay Bhattacharya, MD-PhD, has no research as a physician or biomedical scientist.

Part the Third: More on Malaria. In the movement to Make America Great Again, the country with the largest biomedical research establishment is pulling back from its place in the world because foreign aid has become foreign to our polity. From Science on August 7th: Losing protection The United States helped beat back malaria in Guinea. Now, the disease is set to soar:

Guinea—One morning in mid-June, a 10-year-old boy named Mohamed Camara was lying on a bed in a health center in the small Guinean town of Tamita, wearing bright blue shorts and an army-style T-shirt with Chinese characters on it. He looked listless and feverish; little pearls of sweat flowed from his forehead. He had just been diagnosed with malaria.

That morning, Mohamed’s parents had taken him to the center, which sits about 20 kilometers from the Atlantic coast in Boffa prefecture. Now, they and his baby sister were sitting on the bed next to him, looking anxious. “We were very worried,” said his father, Alseny Camara. They would have brought their son to the hospital earlier, he noted, but his job as a driver had taken him away from home for a few days.

Just 6 months earlier, Mohamed’s parents would have been able to call a community health worker when he got sick. That person might have come to the Camaras’ home on a motorcycle, taken a drop of blood, and applied it to a rapid diagnostic test, which looks a lot like a home test for COVID-19. After the thin line indicating a malaria infection had appeared, the health worker would have given the boy a first dose of drugs and explained to his parents how to continue the treatment. (If his symptoms were severe, Mohamed would have been referred to the health center instead.) A few days later, the worker would have checked in to see how Mohamed was doing.

Community health workers—laypeople trained to provide a few primary health services—are an essential part of the medical system in many African countries, and they’re particularly important in the fight against malaria, when a few days’ delay in diagnosis and treatment can make the difference between life and death. In Guinea, where the country’s entire population of more than 14 million is at risk of malaria, thousands of these workers lost their jobs after the United States suddenly froze billions of dollars in foreign aid in January, just days after President Donald Trump took office.

It turns out that Mohamed did not have a severe case of malaria and has been discharged from the hospital. But the United States of America cannot afford to send the $15M to Guinea that would save countless lives from the scourge that is malaria?

This, is what we have come to under Project 2025?

Part the Fourth: De-Extinction? No, Not Really. As has been all over the news, a company in Texas claims to have de-extincted the dire wolf, a canid that disappeared from the Americas during the last Ice Age:

For months, researchers in a laboratory in Dallas, Texas, worked in secrecy, culturing grey-wolf blood cells and altering the DNA within. The scientists then plucked nuclei from these gene-edited cells and injected them into egg cells from a domestic dog to form clones.

They transferred dozens of the cloned embryos into the wombs of surrogate dogs, eventually bringing into the world three animals of a type that had never been seen before. Two males named Romulus and Remus (get it!) were born in October 2024, and a female, Khaleesi, was born in January.

A few months later, Colossal Biosciences, the Texas-based company that produced the creatures, declared: “The first de-extinct animals are here.” Of 20 edits made to the animals’ genomes, the company says that 15 match sequences identified in dire wolves (Aenocyon dirus), a large-bodied wolf species that last roamed North America during the ice age that ended some 11,500 years ago.

A technical tour de force? Yes. The recovery of an extinct species? No. The Nature article This company claimed to ‘de-extinct’ dire wolves. Then the fighting started is available at the archived link. The meaning of de-extinction is bound up in science fiction, some of which endures in the cinema:

De-extinction is an emerging field that represents the meeting point of several groundbreaking biotechnologies: ancient genomics, cloning and genome editing, ostensibly in the service of conservation. The field has roots in science fiction, with the term seeming first to have appeared in a 1979 novel by Piers Anthony called The Source of Magic. And Michael Crichton’s 1990 novel Jurassic Park — itself inspired by ancient-DNA investigations — popularized the possibility that long-dead organisms could be cloned from preserved DNA.

I have never been much of a reader of science fiction, but I read Jurassic Park in one sitting, just as I did The Andromeda Strain as a teenager. Crichton had a way. I willingly suspended disbelief that DNA would survive intact in blood cells of a dinosaur amber for 65+ million years in a mosquito trapped in amber. And that this would allow the brilliant technicians working for Richard Attenborough to clone Velociraptor and T. rex, among others. It was a good story and the first movie was a good movie (I have not seen any of the sequels). Could DNA survive for 10,000 years in a frozen carcass? Perhaps. Probably, under perfect conditions. Could this DNA be used to clone an organism in a surrogate mother? Very unlikely.

What Colossal has done is, according to Tom Gilbert of the University of Copenhagen, produce a dog with twenty dire wolf genome edits in its genome. Again, this is a marvelous technical achievement that likely has relevance to conservation of endangered species. But this dog not a dire wolf. Still, what this overall approach could do is save the white rhinoceros, which has been hunted to near extinction. By any reasonable definition beyond a parlor trick, de-extinction must include reintroduction of the saved animal into its ecological niche. This is possible with the rhino. The Ice Age of the dire wolf and other large terrestrial mammals, unlikely.

And then there is this:

The company, now valued at around US$10 billion, has attracted celebrity investors, including the media personality Paris Hilton and film director Peter Jackson, alongside a handful of leading scientists as staff and advisers.

Clearly the company is by current definition a bountiful success. And this:

From Colossal’s perspective, the dire-wolf announcement was a success. Lamm says that the company tracked thousands of articles and social-media mentions about the achievement using artificial intelligence, and that they are overwhelmingly positive. “I wouldn’t change one thing,” he says. In July, Colossal announced controversial plans to de-extinct moas, a group of giant flightless birds that vanished not long after humans first arrived in New Zealand.

So, there you have it. Colossal is worth $10B (and we know how that often goes) and the responses to their breathtaking news has been “overwhelmingly positive” according to AI. John Hammond could not have said it better. But the fact remains that science by press release is not science. And extinction still is forever.

Part the Fifth, By Way of Diversion. Big Brother placed the final scene from the movie The Right Stuff in the sidebar of a video I was watching earlier this week. I was seven years old when Gordon Cooper made that final Mercury flight, so I am a sucker for such things. Throughout the remainder of elementary school, we watched virtually every Gemini Program launch on the snowy televisions on the mobile stands in my school (Grades 1-6). Yes, initially the US space program was a response to the Soviet Union. But it was also an unparalleled technical and scientific achievement with national purpose, perhaps similar to the final development and release of the polio vaccines contemporaneous with the Mercury Program.

This was also when the CEOs of General Electric and General Motors, both named Charlie Wilson, were proud their companies were best at what they did and the largest employers in the United States, while providing a living wage and setting that standard across the country. Not that they particularly cared for unions, but their shareholders were virtually inconsequential to them and certainly had little to do with their compensation. The America of 60+ years ago could do stuff and make things. Yes, prosperity was unevenly distributed, but that could have been remedied. After some discussion, a friend sent me this video clip from The Right Stuff, and commented, “This is where it started to go wrong.” He is correct. The NASA recruiter played by Harry Shearer may be the first member of the Professional Managerial Class (PMC). The older man in the cameo behind him is Chuck Yeager, who was played in the movie by Sam Shepard.

Those with experience, knowledge and knowhow, independence, and courage “don’t fit the profile.” Sums up America’s current state in four words.