A Bold Idea for the NIH

Too many people don’t believe anymore in the American dream.

But if you can’t dream big, you can’t accomplish big things.

Today, I’d like to propose a bold idea for the future of biomedical research.

Let’s triple the National Institutes of Health budget over the next decade.

Impossible? Hear me out.

We know the NIH, with a $41.7 billion a year budget, is a force for human health and the economy. It has catalyzed the economy for decades.

Think about the Human Genome Project. Criticized as a costly boondoggle in the 1990s, it morphed into a seed investment for the ages. It cost $3.8 billion between 1990-2003. What did we get? Through 2010, the estimated economic impact was $796 billion, according to Battelle.

That’s $141 of economic activity for every $1 invested by the US government. That’s right — a 141x return on investment!

The dividends don’t stop there. That calculation was made in 2010. Biotech would be in the dark ages today without that DNA code on every desktop, and the ability to sequence DNA at high speed and low cost. You can draw a straight line between that catalytic investment by the US government (and to a lesser extent the UK, France, Japan and others), and biopharma’s invention of mRNA vaccines for COVID-19.

That is one success story. There are many others.

The NIH, composed of 27 institutes, supports the best work in cancer, infectious disease, neuroscience, mental health and other fields.

Ordinary citizens in the US have no idea that our taxpayer dollars can have this kind of impact. They have no idea that when we send our $41.7 billion to Washington for the NIH, 85 percent of that money comes right back to the states that are home to so many vibrant universities.

People have no idea that the NIH money is divvied out on a competitive, merit-based grant review system. Often, they are surprised to learn it doesn’t go in the pocket of some Congressman’s son-in-law.

They have no idea that the institutes themselves are led and staffed by brilliant hard-working people like Tony Fauci. They are surprised to learn he’s more than a good talker on TV. They are surprised to learn he got his job because he was the 13^th most cited scientist in the world from 1983-2002.

People have no idea that you and me — the US taxpayer — are by far the most powerful investors in biomedicine. No country in Europe invests at this magnitude. China? It has ambition. But it envies the NIH system, seeks to copy it, and knows it has a long way to go.

Citizens in the US tend to have an exaggerated view of what billionaires like Bill Gates and Warren Buffett can do. Drinking from the poisoned chalice of political entertainment media for far too long, we’ve internalized the idea that government is full of screw-ups, and business titans like Gates and Buffett are the true wellsprings of science and innovation.

Generous as they are, their impact pales by comparison to the US taxpayers. The Bill & Melinda Gates Foundation, the world’s largest philanthropy, invests $5 billion a year across all its programs that include education, global development and global health. The NIH pumps $41.7 billion into biomedical research alone for the American people. The Gates Foundation knows this, and it’s why they are always talking about partnerships. They know the NIH is the beating heart of biomedical research.

We as a country just don’t fully appreciate what a gem we have in the NIH.

In my state of Washington, the late Sen. Warren Magnuson brought home the bacon that built the University of Washington Health Sciences Center and the Fred Hutchinson Cancer Research Center. These are sparkling stars in my community, and in the global scientific enterprise.

Sen. Magnuson operated in the optimistic post-WWII era, guided by FDR’s science advisor, Vannevar Bush. It’s worth re-reading that seminal document “Science, the Endless Frontier.”

It’s worth noting that in 1945, when Bush wrote that visionary document, we hadn’t even discovered the double helix structure of DNA.

So what could we do with a reinvigorated NIH?

A couple thoughts:

1. A new NIH intramural campus, located West of the Mississippi. The NIH campus in Bethesda, Maryland currently has about 6,000 research scientists. I’m thinking of a new 5,000 or 6,000-scientist campus in a Midwestern or Western city. It could be an attractive place for young families, a place with affordable housing, cultural amenities, existing biomedical building blocks, and good transportation bones to handle an influx of newcomers. St. Louis would work. It’s the home of Washington University in St. Louis, it’s the Gateway to the West, and a major American city that has lost 65 percent of its population since its peak in 1950.

Why do this? Planting a major research stake in the ground, outside of Washington DC, New York, San Francisco or Boston could have multiple benefits. We would get good bang for our taxpayer investment, with lower operating and capital expenses. A new NIH campus would spur surrounding economic development with housing, transportation, small business. It would send a powerful cultural message that this 21st century industry creates shared prosperity, not just prosperity for a few coastal cities.

Putting an NIH campus in St. Louis would give young scientists a place to spread their wings and get established – where they could make the same wage as in a place like Bethesda but where their salary would support a higher standard of living. Not only that, but a fresh new campus would create some healthy competition for Bethesda, and help bust out of moldy Groupthink patterns of thought.

A St. Louis NIH campus could attract fresh new thinkers. I’m reminded of Nobel Laureate Mario Capecchi, who left Harvard University to go to the University of Utah to get away from some of the suffocating aspects. At Utah, free to do his own thing, he invented knockout mouse technology. (Capecchi, by the way, is a Holocaust survivor, and orphan, who found refuge in the US. He’s a poster boy for immigration reform, but that’s another column.)

2. Build up four new cornerstone institutes of the NIH. We could support areas that need more basic research. I’m thinking of a reborn National Institute of Infectious Disease ($5.8 billion annual budget), a beefed-up National Institute of Mental Health ($2 billion), and a more generously funded National Institute of Neurological Disorders and Stroke ($2.4 billion). The “allergy” part of Fauci’s group at NIAID could be reorganized under a new, independent National Institute of Immunology. This is worth housing in an independent institute because immunology is so full of possibility, and we need more young people growing up in the field.

Why do this? These institutes are traditionally underfunded, especially compared with the big dog at NIH – the National Cancer Institute ($6.6 billion annual budget). But look at the future of disease burden. There’s SARS-CoV-2 and flu and malaria, TB and HIV. Then depression and anxiety and schizophrenia and bipolar disorder. Then Alzheimer’s and Parkinson’s and multiple sclerosis.

We’re talking about diseases affecting tens of millions of people worldwide.

Biopharma invests little in these areas because these fields are less mature than cancer, and because there’s less government-funded basic research to build on. There simply are not a lot of promising, short-term angles for industry R&D to attack. That was true for cancer in 1970. But then President Nixon and leaders in Congress (including Sen. Magnuson) made a big bet on the National Cancer Institute. That investment is paying dividends today.

This week, while mulling the state of our divided country, I listened to a podcast with former Sen. Bill Frist (listen here). He’s a Republican from Tennessee, a heart surgeon by training. NIH director Francis Collins was his guest. Frist, reminiscing about the Human Genome Project, marveled at how it came in ahead of schedule and under budget.

Then he asked Collins about the NIH budget.

Collins rattled through the basics. The NIH budget doubled in a bipartisan push from 1998-2003. Then things stalled. Only one-fifth of grant proposals get funded, leaving a lot of worthy projects on the cutting-room floor, Collins said. By 2015, Congress took notice, setting aside cash for “inflation-plus 5 percent” budgets. Collins sounded happy with this progress.

Certainly, “inflation plus 5 percent” is better than the 25 percent annual budget cuts that President Trump proposed. Congress, wisely, overruled him.

But we can do better than “inflation plus 5 percent.” We are in a biology renaissance. The needs for human health are enormous, and growing. The US government is by far the most powerful force in the world for this kind of catalytic investment. The NIH is capable of creating entirely new industries, like genomics.

With NIH as the foundation, along with a vibrant biotech industry, the US should be able to create hundreds of new drugs and diagnostics and vaccines over the next 100 years. We have a generation of talented young people that are yearning for purpose and meaning in work.

Let’s shake off the cynicism, pessimism and stale thinking that has infected our country in recent years.

Let’s triple the NIH budget. Let’s continue to lead the world in biomedical research.

 

Vaccines

• Moderna on Track to Make 100 Million Doses of Vaccine by End of March, CEO Says. WSJ. Jan. 19. (Peter Loftus)
• Model-informed COVID-19 vaccine prioritization strategies by age and serostatus. Science. Jan. 21. (Kate Bubar et al)
• How Fast Can Vaccination Make a Difference? Look at Israel. The Economist. Jan. 23.
• Allergic Reactions Including Anaphylaxis After Receipt of the First Dose of Pfizer-BioNTech COVID-19 Vaccine. JAMA Insights. Jan. 21. (Tom Shimabukuro, Narayan Nair)
• SARS-CoV-2 Vaccines: Much Accomplished, Much to Learn. Annals of Internal Medicine. Jan. 19. (Mark Connors, MD, Barney S. Graham, MD, H. Clifford Lane, MD, Anthony S. Fauci, MD)
• Let’s Not Forget, We Have a Phase III COVID-19 Vaccine Readout Coming Soon from J&J.
• 

Science of SARS-CoV-2

• SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma. BioRxiv. Jan. 19. (National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa team)
• Severely ill COVID-19 patients display impaired exhaustion features in SARS-CoV-2-reactive CD8+ T cells. Science Immunology. Jan. 21. (Anthony Kusnadi et al)
• Sex Differences in Immune Responses to COVID-19. Science. Jan. 22. (Takehiro Takahashi and Akiko Iwasaki)
• Effect of Bamlanivimab as Monotherapy or in Combination With Etesevimab on Viral Load in Patients With Mild to Moderate COVID-19. JAMA. Jan. 21. (Robert L. Gottlieb et al)
• The hygiene hypothesis, the COVID pandemic, and consequences for the human microbiome. PNAS. (Brett Finlay et al)
• mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants. BioRxiv. Jan. 15. (Zijun Wang et al)
• Household transmission of SARS-CoV-2 and risk factors for susceptibility and infectivity in Wuhan: a retrospective observational study. The Lancet Immunology. Jan. 18. (Fang Li et al)

Public Health

• Outgoing CDC Director Warns We’re Heading Into the ‘Worst of it.’ NPR. Jan. 15. (Mary Louise Kelly)
• Europe’s Growing Mask-Ask: Ditch the Cloth Ones for Medical-Grade. Washington Post. Jan. 20. (Loveday Morris)

Features

• Another Way to Protect Against COVID-19, Beyond Masking and Social Distancing. Indoor Humidity. Scientific American. Jan. 19. (Akiko Iwasaki)
• Patients Fend for Themselves To Access Touted Antibody Therapeutics. Kaiser Health News. Jan. 20. (JoNel Alecia)
• Rogue Antibodies Could Be Driving Severe COVID-19. Nature. Jan. 19. (Roxanne Khamsi)

Policy & Politics

• A ‘Tsunami of Randoms’: How Trump’s COVID Chaos Drowned the FDA in Junk Science. Vanity Fair. Jan. 19. (Katherine Eban)
• Signs of Hope in Joe Biden’s Science Advisor. The Bulwark. Jan. 16. (David Shaywitz)
• National Security Directive on United States Global Leadership to Strengthen the International COVID-19 Response and to Advance Global Health Security and Biological Preparedness. WhiteHouse.gov. Jan. 21. (The White House)
• New CDC Director Pledges to Speed Vaccination, Restore Trust in Agency. WSJ. Jan. 19. (Betsy McKay)
• COVID-19 Vaccine Leaders Waited Months to Approve Distribution Plans. WSJ. Jan. 15. (Betsy McKay, Rebecca Ballhaus and Stephanie Armour)
• Mark Cuban Is Going to Help Pharma’s Image. Forbes. Jan. 19. (John LaMattina)

Our Shared Humanity

• If You’re Offered a Vaccine, Take It. NYT. Jan. 21. (Melinda Wenner Moyer)
• Ideaya, Spelman College Team Up to Provide Young African-American Women a Steppingstone to Biotech Careers. FierceBiotech. Jan. 19. (Amirah Al Idrus)

Financings

Cambridge, Mass.-based Beam Therapeutics, the developer of DNA base editing for drug development, raised $260 million in a stock offering at $93 a share. The developer of this early-stage technology is now valued at more than $5 billion. It has been buoyed in part by intriguing results by one of its partners, Verve Therapeutics, which uses base-editing for a single-shot gene therapy that has shown an ability to lower cholesterol in non-human primates.

Speaking of base-editing, Cambridge, Mass.-based Verve Therapeutics raised $94 million in a Series B venture financing led by Wellington Management and co-led by Casdin Capital. The company plans to enter the clinic in 2022 with its gene-editing therapy aimed at PCSK9 for patients with heterozygous familial hypercholesterolemia. It’s a genetic disease that causes extremely high levels of cholesterol that raises the risk of heart attack, stroke and death. (Listen to CEO Sek Kathiresan on an upcoming episode of The Long Run podcast).  

South San Francisco-based Vera Therapeutics, the developer of treatments for autoimmune and inflammatory diseases, raised $80 million in a Series C deal. Abingworth led. The company is developing atacicept, in-licensed from Merck KGaA, and is being run by a team of drug developers formerly with Gilead Sciences.

Plymouth Meeting, Penn.-based Inovio, the DNA vaccine developer, raised $150 million in a stock offering at $8.50 a share.

South San Francisco-based CytomX Therapeutics, the developer of antibody drugs for cancer, raised $100 million in a stock offering at $7 a share.

Cambridge, Mass.-based Editas Medicine, the genome editing therapeutics company, raised $231 million in a stock offering at $66 a share.

Waltham, Mass.-based Dyne Therapeutics raised $168 million in a stock offering at $28 a share. The company is developing treatments for muscle diseases.

Durham, NC-based Chimerix raised $100 million in a stock offering at $8.50 a share.

Bothell, Wash.-based Athira Pharma raised $90 million in a stock offering at $22.50 a share. It’s working on small molecule drugs for neurodegenerative diseases.

San Francisco-based Invitae said it’s raising $400 million in a stock offering to support its genetic testing.

Lexington, Mass.-based Aldeyra Therapeutics raised $75 million in a stock offering at $9.50 a share. It’s working on immune-mediated diseases.

Cambridge, Mass.-based Syros Pharmaceuticals raised $75.6 million in a stock offering at $14 a share. It’s working on medicines based on controlling gene expression.

Cambridge, Mass.-based TCR2 Therapeutics, the developer of T-cell therapies for cancer, raised $140 million in a stock offering at $30.50 a share.

Cambridge, Mass.-based Fulcrum Therapeutics raised $44 million in a stock offering at $11 a share. (TR coverage of Fulcrum, September 2018).

San Diego-based Plexium raised $35 million in a Series B financing to develop protein degrading drugs. Lux Capital and Pivotal BioVentures led, with participation from The Column Group.

Deals

South San Francisco-based Twist Bioscience, the DNA synthesis company, struck a pair technology partnerships. One, with Serotiny, allows it to make Chimeric Antigen Receptors for CAR-T cell therapies. Another deal with Applied StemCell provides access to Chinese Hamster Ovary cell technology for making antibody therapeutic candidates.

Emeryville, Calif.-based Gritstone Oncology, a personalized neoantigen therapeutics developer, secured a licensed from the La Jolla Institute for Immunology to incorporate additional epitopes into a new SARS-CoV-2 vaccine candidate, potentially making it harder for the virus to develop escape mutations. The National Institute for Allergy and Infectious Disease and Bill & Melinda Gates Foundation are supporting the work.

Servier and MiNA Therapeutics agreed to work together on small activating RNA therapies for neurological diseases.

Thermo Fisher Scientific agreed to acquire Mesa Biotech for $450 million in cash upfront. The small company does PCR point of case testing for infectious diseases.

Eli Lilly agreed to work with Netherlands-based Merus on T-cell engaging bispecific antibodies for cancer. Merus will get $40 million in upfront cash, plus a $20 million equity investment from Lilly.

Personnel File

Eric Lander, the leader of the Broad Institute, was appointed to be science advisor to President Joe Biden, and head of the Office of Science and Technology Policy. The OSTP was also elevated to a Cabinet-level position, increasing the clout of science in the new administration. Read Biden’s letter to Lander, filled with questions on important scientific matters for the years ahead. (Science coverage)

BIO CEO Michelle McMurry-Heath announced her new team, and leadership structure.

Cambridge, Mass.-based Foundation Medicine said CEO Cindy Perettie is moving over within the Roche group of companies to lead the Molecular Lab Solutions business at Roche Diagnostics in Pleasanton, Calif. Brian Alexander, the chief medical officer, will lead Foundation Medicine until a permanent CEO takes over at Foundation Medicine.

Bristol-Myers Squibb’s head of hematology, Nadim Ahmed, left the company after the company failed to win FDA approval of its liso-cel CD-19 directed cell therapy by Dec. 31. Reported by FiercePharma.

Cambridge, Mass.-based Cerevel Therapeutics, the developer of drugs for neurodegenerative diseases, named Deval Patrick and Deborah Baron to its board of directors.

South San Francisco-based Trishula Therapeutics named Anil Singhal as its new CEO. The company is developing a CD39-directed antibody for cancer.

San Diego-based Avidity Biosciences, the developer of antibody-oligonucleotide drugs, named Michael Flanigan as its chief technical officer.

Cambridge, Mass.-based Black Diamond Therapeutics named Kapil Dhingra to its board of directors.

Regulatory Action

Daiichi Sankyo and AstraZeneca won FDA approval for fam-trastuzumab deruxtecan-nxki (Enhertu), a treatment for locally advanced or metastatic HER2 positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen.

Janssen Pharmaceuticals won FDA approval for daratumumab and hyaluronidase-fihj (Darzalex Faspro) for newly diagnosed light chain amyloidosis. It’s a subcutaneous form of Darzalex.

Merck won FDA approval for vericiguat (Verquvo) for heart failure patients.

Tweetworthy

Science is back in the saddle, and serious people are back in charge at the top of the US government. Thank God.