Nobel art of science

Santiago Ramón y Cajal’s drawings lay out the brain in surprising detail—and beauty.

“An entire universe that has scarcely been explored lies before the scientist… Each cell presents us with the unknown, and each heartbeat inspires profound meditation within us.”

He grew up in poor Spanish hill towns near the French border, bright, impulsive, strong-willed, prone to escapades that have more than a touch of the medieval. He was endlessly curious, experimental, energetic, determined to think things through by himself. By eight years old he was drawing incessantly wherever he could, coloring his drawings with paint flaked from walls, bitterly opposed by his doctor father. He was a famously disobedient student, often beaten by teachers, once locked up by himself for more than a day. His father pulled him out of school and apprenticed him to a shoemaker for a year. He was an enthusiast and expert for drawing, painting, birds, nature walks, wooden cannons he built himself. Years later, he plunged deeply into gymnastics, chess, gymnastics, philosophy, hypnotism and whatever else caught his interest. When he grew excited by photography, he not only taught himself excellent shooting skills but developed emulsions for developing prints that were better than what he could buy. He and his father stole bones from a graveyard to help their anatomy studies. He joined the Spanish army as it fought rebellions at home and in Cuba. He survived malaria and then tuberculosis.

Such was the education of Santiago Ramón y Cajal, the world’s greatest neuroscientist.

He won the Nobel Prize in 1906 and is best known for his theory that nerve cells in the brain are not directly wired together but connected by chemicals—a theory not confirmed until the electron microscope debuted, decades later. He possessed an astonishing intuition for guessing at brain function based on structure, backed by an astonishing amount of hard work to reveal that structure. He couldn’t afford a good microscope until he was given one for his help in a cholera epidemic. He taught himself German, the language of biomedical science, to keep in touch with the latest findings. He published his own scientific journal when it was the only way to spread his own discoveries, which were numerous and major.

Perhaps most famously, Ramón y Cajal presented what he saw in the brain in thousands of drawings that elegantly show the brain’s wild menageries under the microscope, artwork that is stunningly created to emphasize structure and concepts. You can now see 80 of these masterpieces in the well-received Beautiful Brain exhibition at the MIT Museum.

Ramón y Cajal lived in a very different time—for instance, his autobiography has nothing but good to say about his wife but never mentions her name. He was not just genius but appealing human being. He was thoughtful, kind, wryly humorous, sociable, patient with others, resourceful, surprisingly tough, endlessly curious.  He wrote superbly on science and his own remarkable life. His aphorisms are still quoted. His lessons still stand.

“Drawing enhances discipline and attention, for it forces us to observe the totality of the phenomenon and see details overlooked in ordinary observation.”

“In our parks are there any trees more elegant and luxurious than the Purkinje cell from the cerebellum?”

“Nature is a harmonious mechanism where all parts, including those appearing to play a secondary role, cooperate in the functional whole.”

Raging hormone

Why is insulin so expensive in this country?GoFundMe insulin

We run on sugar, and sugar needs insulin to get into our cells. It’s no surprise that insulin was the first genetically engineered drug, approved by the FDA in 1982. Synthetic insulin keeps millions of people with type 1 diabetes, and a greater number of people with type 2 diabetes, alive.

Basic research keeps turning up surprises about the hormone—its starring roles in the brain, for instance, and its production by some viruses.

Drug companies mostly focus, though, on fiddling with how quickly the body absorbs it. Insulin variants that work either very quickly or very slowly are very important, but why can’t we have insulin that doesn’t need refrigeration? Or “smart insulin” that responds to blood glucose levels, first proposed when Jimmy Carter was president? Although Sanofi supports interesting projects aimed at smart insulin, as do the other market leaders Novo Nordisk and Lilly, there’s little visible progress toward the clinic.

But the biggest question about insulin is: Why is it so expensive in this country?

A 2016 study published in JAMA, for instance, showed that insulin costs doubled between 2002 and 2013. This trend is only accelerating, because there’s no price competition. Irl Hirsch, an endocrinologist at the University of Washington, summarized the story well in an ADA presentation back in 2016 and his points still apply. Year after year,  extremely profitable drug makers and pharmacy benefit managers point their fingers at each other. But as Hirsch noted, “we can point our fingers at everyone.”

New entries such as Basaglar, the first biosimilar insulin approved by the FDA, delayed by predictable patent battles but now available, don’t seem to change the story.

And the story has plenty of human faces. Among them was Shane Patrick Boyle, who died a year ago, unable to raise the money to buy insulin for his type 1 as he saved up for his mother’s funeral. Look at GoFundMe today to see similar personal pleas for help.

As with every other problem in healthcare cost, there are no simple solutions.

One new approach comes from the Open Insulin Project and similar biohacking groups that are making worthy efforts to create generic insulins. But those are  only early steps in the process, and clinical trials are too expensive to crowdfund.

You can argue that in a more rational world, the federal government would step in. Why not launch a 28th National Institute of Health that develops selected high-value high-need generics and biosimilars, brings them through clinical testing and into the clinics? Or simply control the costs of crucial drugs, lowering prices in the years after generics or biosimilars enter the market, as Australia apparently is now doing? OK, not likely. But what actually would help?

 

Celling out cancer

As immunotherapies start to change clinical practice, we hope for more.

CI_cover_crop

For a blockbuster drug, pembrolizumab comes with a strange history, nicely told here by David Shaywitz.

Pembro is a “checkpoint inhibitor”, a biologic designed to take the brakes off T cells so that they can wipe out tumors. Back in 2014, it was the first drug that targets the PD-1 protein on the surface of T cells to get FDA approval. Also now known as Keytruda, pembro has received FDA green lights for many kinds of cancers. It accounts for billions of dollars each year and is in more than 500 clinical studies.

But it was born in a small Israeli biotech trying to develop treatments for autoimmune diseases by putting brakes on T cells (yes, the reverse of checkpoint inhibition).  The small biotech that created pembro and realized it was a promising cancer drug candidate was soon bought by a larger pharma firm, which was then acquired by Merck & Co. As Shaywitz notes, the giant pharma shut down development not once but twice, before successful trials of other checkpoint inhibitors changed its mind.

Today pembro comes as a colorless liquid in a small IV pouch, looking very much like saline solution. It lists at around $50 a milligram, one case in point for the extremely real concern about how any country can pay for such drugs as they start to become standard of care.

You don’t think about costs, however, if you’re in a clinic as I was earlier this month, watching a friend with metastatic melanoma joke with the nurse hooking up his IV. You just hope the treatment works.

It’s been a pleasure to edit this month’s Nature Outlook on cancer immunotherapy. Many thanks to the outstanding authors, editors and designers who put it together! And to Elin Svensson, who created the great cover art above.

Pub read

It’s a golden age for magazines on science and the environment.

Each year as I help to filter out the National Association of Science Writers’ Science in Society Awards nominees, I run across remarkable new-to-me publications.  You could spend wholly unworkable amounts of time on their dazzling stories and videos.

Some of these magazines seem to generate cash (Quartz offers one clue: sponsored content that you actually might want to read.) But most of the pubs run on institutional funding and/or donations, which is not always a recipe for long-term survival. Here are a few favorites, each with a story or two picked fairly randomly (except that I wrote two of them).

Aeon, Votes for the future
Ensia, Could this one simple idea be the key to solving farmer–environmentalist conflicts? and With storms intensifying and oceans on the rise, Boston weighs strategies for staying dry
Hakai, Damming Eden
High Country News, Why western wildfires are getting more expensive
Mongabay, Abandoned by their sponsors, Madagascar’s orphaned parks struggle on
Pacific Standard, Libya’s slave trade didn’t appear out of thin air
Quanta, Artificial intelligence learns to learn entirely on its own
Quartz, AI is now so complex its creators can’t trust why it makes decisions
Sapiens, Sea level rise threatens archaeological sites
Undark, The allure and perils of hydropower and Putting digital health monitoring tools to the test

Towers of power

Wind turbines go to work 16 miles off the Rhode Island coast.

Offshore wind turbines seemed a bit, well, gimmicky to me until a few years ago when I saw a farm calmly spinning its blades as I flew home from Europe. Anything that keeps working in the North Sea is entirely real. Now they have arrived in 600-foot-form off the New England coast, as I saw last month in a trip to Deepwater Wind’s installation off Block Island (thanks, Noelle Swan and the New England Association of Science Writers!). These giant beasts won’t always be easy to maintain, as we saw watching a crew struggling to jump onto one tower from a support vessel in gentle six-foot swells from Hurricane Maria. The 240-foot blades are no favor to offshore birds. But Deepwater Wind seems to have made every reasonable effort to minimize and monitor the overall environmental impact of the turbines, as attested by the National Wildlife Federation scientist onboard our fast ferry. Ocean wind turbine technology is advancing rapidly, one example being the replacement of the traditional gearbox with a GE direct-drive permanent magnet generator, noted Willett Kempton of the University of Delaware’s ocean wind power program. Wind turbines can tap steady winds at sea, where they can be built much larger than on land, and a wealth of projects are planned along the U.S. east coast. Yes, they’re designed to survive hurricanes, although maybe not a problem like Maria. And although offshore wind still can’t produce power here as cheaply as fossil-fuel plants, European wind costs are already below that mark.

Public Spectacle

A beacon of hope in a changing climate.

kid Spectacle

On a clear hot August day you can take a ferry to Spectacle Island and walk a winding path up to its northern summit, admiring wildflowers and eating blackberries. The summit is the highest point of land on Boston Harbor, with low wooded islands scattered around.

Off to the east you can spot a windmill near the huge sludge-digesting eggs of Deer Island, and a second windmill a few miles south at the tip of the Hull peninsula. These two points of land bracket the entrance from Massachusetts Bay to the harbor’s inner archipelago.

One distant day, Deer Island and Hull also may anchor a massive sea barrier, holding off an ocean that’s now projected to climb as much as eight feet by 2100.

Today it’s hard to imagine how we might start to build such a Big Dike, given our current politics.

But you can also see hopeful signs on this Spectacle for our ability to clean up our own messes.

The first time I sailed past the island it was a garbage dump, with the remnants of a horse-rendering plant buried under many feet of still-smoldering refuse.

Now that’s all taken away and replaced by fill from the Big Dig. The island was reengineered and replanted. Rich ecosystems began to reappear. On summer days like this, children swim a stone’s throw away from the site of the old factories.

In wildness is the preservation of the world, as Thoreau said. But not just in wildness.

Blossoms in biomedicine

The remarkable global push for cancer immunotherapies.
El_Talayón.byJose Ignacio Martinez Navarro
Editing a Nature special report on cancer immunotherapies, I’m struck most by the sheer scale of the development effort. Something like 3,000 clinical trials are underway, 800 of them combining treatments. The FDA has approved five checkpoint inhibitors, designed to unleash T cells against tumors. The agency seems close to approving the first CAR-T cell treatment, in which a patient’s T cells are removed, reengineered to attack cancer cells, regrown in volume and returned to the patient. Old dogs of immunotherapies are learning new tricks. Some newer approaches are getting much attention—notably personalized neoantigen vaccines, in which individual tumors are sequenced to give clues on how to best target their unique sets of immune-system-alarming antigens. Some clinical trials fail, some do surprisingly well.  The competition is more than intense and trials are not always carefully planned or analyzed. But the landscape is changing.