Keeping the Golden Age of Biology Golden

A personal perspective, an opportunity, and an invitation

Updated Intro: This article was originally drafted in September 2023, before I had begun using email delivery from Substack. It is a more personal note about the future of scientific funding and cancer research. I’ve been advised it’s best to include “calls to action” and personal narrative upfront, but this article is about the journey…for the specific details, you can skip to the end where the links and description are. Perhaps I’m more Russian author than management consultant…

Last week I joined a team of intrepid biotech leaders in an ambitious effort to raise $1M to support early career investigators in their pursuit of bold and innovative ideas to tackle cancer.

It is my first time undertaking such an endeavor and part of me wondered why.

Over the weekend I began crafting messages to colleagues, friends, and family telling them about the goals and inviting them to join me. I was advised by the organizers to make the message personal to create a more compelling story. I knew internally why I was attracted to this cause, but I had not yet really made it clear to others. This brief article is an attempt to do that — and alongside, extend an invitation to others to join us.

Living in the Golden Age

It’s hard to fathom how much has transpired in biology in the last few decades. The sequencing of the human genome, the million-fold reductions in NGS costs and the introduction of genomics into routine clinical practice, the transformation of genome engineering and CRISPR, the precision engineering of cells and the human immune system, the advances in machine learning…

It has been extraordinary. We are living in a golden age.

Yet none of these advances were obvious or foregone conclusions — they all existed at some point on the margins, in the shadows.

Transformative innovation begins less often with a “Eureka” than a “huh…that’s weird”

CRISPR was a series of seemingly random observations of repeated genetic sequences in bacteria…”that’s weird”. Blood plasma used to be routinely discarded from blood samples as not being important until it was discovered that it harbored tiny fragments of DNA that could be used as a liquid biopsy of internal processes. We are still figuring out intricacies of the human genome 20+ years after the flagship project.

Over the last few decades, these corner cases, pursed with abandon, have transformed health care, and cancer care in particular.

We can now precisely engineer our immune system to effectively cure cancer. We can now take a sample of blood and screen for, monitor, and determine appropriate therapeutic treatment paths for a whole host of cancers non-invasively. And we are just beginning.

The Future Is Accelerating at the Front

Science often takes a long time to mature — it is “standing on the shoulders of giants” but those timelines are being compressed along with the broader transformation in technology. Things are speeding up.

What does this mean?

Simply that ideas will come faster and from more corners than ever as disciplines merge, interconnect and accelerate. We are seeing this first hand with the collision of machine learning and biology. Entire new disciplines are being created at the margins and intersections. Computational biology in its current form (incorporating deep learning, multi-omics and so forth) is arguably a brand-new discipline just in the last decade.

It is worth noting that CRISPR/Cas9 and AlexNet were both published in 2012. The intersection of biology and deep learning is a growing frontier.

And the flag bearers of this future are the newly minted investigators — those pursuing the ephemeral leading edge of knowledge.

The Funding Machine is Lagging

The bread of butter of scientific research is funding — and the main metric is the R01 grant from the National Institutes of Health. There has been a lot written about the increasingly competitive nature of these grants in general, but somewhat less written about the distribution. For decades, principal investigator grants for early-stage investigators have been declining.

Ref: https://nexus.od.nih.gov/all/2012/02/13/age-distribution-of-nih-principal-investigators-and-medical-school-faculty/

Something different is needed — if we do not support the young researchers at the frontier, we will fall behind in the possibilities of the future.

Nobel Prizes are Waiting (updated section)

The 2023 Nobel Prize in Medicine for research into mRNA technology is apropos. The scientific and technical advances have been transformative and ushered in an entirely new class of medicines. Yet, the struggle to acquire support, funding, or acceptance of this research for the young scientists pursuing it was unrelenting to the point that the researchers pursuing this science were demoted and rejected by established institutions.

Yet the perseverance of the science has and will continue to transform the world.

Public grant funding for early career scientists has plummeted, yet the recent Nobel Prize has recognized the importance of supporting these scientists pursuing high risk and high reward research.

The importance cannot be underestimated. It is well stated by Eric Lander in his review of the history of CRISPR in his article “The Heroes of CRISPR”

“It is instructive that so many of the Heroes of CRISPR did their seminal work near the very start of their scientific careers (including Mojica, Horvath, Marraffini, Charpentier, Vogel, and Zhang)—in several cases, before the age of 30. With youth often comes a willingness to take risks—on uncharted directions and seemingly obscure questions—and a drive to succeed. It’s an important reminder at a time that the median age for first grants from the NIH has crept up to 42.

Notably, too, many did their landmark work in places that some might regard as off the beaten path of science (Alicante, Spain; France’s Ministry of Defense; Danisco’s corporate labs; and Vilnius, Lithuania). And, their seminal papers were often rejected by leading journals—appearing only after considerable delay and in less prominent venues. These observations may not be a coincidence: the settings may have afforded greater freedom to pursue less trendy topics but less support about how to overcome skepticism by journals and reviewers.

The Personal Side of Things for me

The history above is one that I’ve lived. I’ve been an early cancer investigator during my 20’s while doing my PhD at the Moores Cancer Center at UCSD. Working daily at a research hospital that blends both clinical and research efforts creates a unique sense of realism.

After my PhD, I’ve lived the transformation of genomics into routine clinical practice at the forefront of the liquid biopsy field — a field that has transformed many areas of cancer research and management and will continue to do so.

I lived the introduction of CRISPR/Cas technology into drug discovery R&D, much of which has led to an explosion in our ability to understand mechanisms of cancer. And further, the development of precision immune cell engineering for the development of potential curative cancer treatment. I’ve met recipients of CAR-T cell therapies that are 10 years cancer free — as living miracles of what is possible.

Seeing the impact of this work has been a very visceral experience. And one that I’m committed to continue to support.

The Personal Side for Everyone

Cancer is one of those things that will likely touch everyone in some way at some point. Over the course of this campaign, I’ve encountered friends, colleagues, and strangers with profound and tragic personal stories of cancer affecting their lives and those of their loved ones. The potential for cancer is baked into our very biology. It’s something that is part of life — at least as we currently live it.

So, What Did I Join?

I’ve been advised that it’s better to put the point upfront, but this article is more about the journey than the destination. If you’ve read this far, hopefully, it has struck a chord, and maybe you’ll want to join us.

The Details:

The group that I joined is part of a series of campaigns known as the Timmerman Traverse — you can see the link to the announcement here

As a group we’re aiming to raise $1M to support the Damon Runyon Cancer Research Foundation — you can find out more about them here — but in summary, they are expressly focused on funding young investigators working on bold and innovative cancer research. The mission:

At the Damon Runyon Cancer Research Foundation, we fund high-risk, high-reward cancer research. We identify and enable young scientists who are brilliant, brave and bold enough to go where others haven’t

They’ve funded over 4,000 scientists since 1946 and have an impressive array of Nobel Prize winners, National Medal of Science winners, and National Academic of Science members in their ranks. And they are a superb foundation (link).

And we’re going to be climbing Mt. Kilimanjaro. It’ll be fun.

This is the call to action

Please Donate to Support the Next Generation of Cancer Researchers- Your Help is Needed

If you’ve found this story compelling and/or believe in a future where cancer is no longer, please take a moment to consider supporting this effort by donating here and sharing this with your colleagues, friends and families

Every bit helps. This is my reason for supporting this effort — hopefully you’ve found one too.

Image credit: https://adnas.com/wp-content/uploads/2016/03/human-biology-scaled.jpg