The Cancer Innovation Engine- Is it slowing down?

HBR has an excellent paper published on the slowing down of the US innovation system. It hasn’t compared the rise of China in this space but is not the point of discussion. It starts off with a pertinent issue:

This slowdown has occurred despite increased investment in scientific research. Data from the National Science Foundation (NSF) indicate that U.S. investment in science has steadily increased between 1970 and 2010, as measured by dollars spent (which has gone up 5X), number of PhDs trained (2X) and articles published (7X). Why is there little productivity growth to show for this?

The rising number of PhD’s probably correlating with the need for more specialists in specific niche domains (but not everyone gets jobs/industry experience). The debate on specialists versus generalists isn’t settled. The paper doesn’t dissect the sectors where the investment is going- addressing the need for palliative care and improving accessibility versus trying to find the next breakthrough molecule because of perverse incentives associated with the patenting regime. Therefore, research has become more lopsided- towards lifestyle diseases versus issues related to the emergence of infections, for example.

I am using the HBR article as a prop and as a starting point for discussion.

Is the development of CRISPR Cas9, for example, groundbreaking? Has it made to the clinics? Have we really understood if the methodologies can be universally accepted?

I think we need to first distance ourselves from the hype cycle heralding the “innovations” as significant breakthroughs. They are not. I am not cynical towards science but only towards the politicisation and extensive marketing. It need not be like that.

This graph is very instructive:

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Large firms’ withdrawal from science can be gleaned from the above chart, which shows that the share of research (both basic and applied) in total business R&D in the U.S. fell from about 30 percent in 1985 to below 20 percent in 2015. While the amount of basic research (the “R” of R&D) stagnated over the 20-year period between 1990 to 2010, total industry spending and patenting on development activities (the “D”) have grown steadily.

The heydays of the corporate-funded research are almost over, and the “shareholders” have effectively sounded the death-knell. It is because university research is de-risked from the market realities. It is easier to propose that CAR-TCell therapy will work in solid tumours (for example) (long story short it doesn’t) and then marshall resources to try and push the envelope for something that doesn’t work because we don’t understand how microenvironment is structured. As radiation oncologists have shied away from basic radiobiology, we have no idea if hypofractionation can “open up the microenvironment” (in brief, yes, it does beautifully). Innovation and application of creative solutions are entirely different but are used interchangeably.

Likewise, genuine innovation was the advancement from orthovoltage to kilo and megavoltage. Everything else was empirical and backed by observation. Intensity modulation was the second epoch of change; everything else is again a creative adaption of technologies (volumetric arc therapies, for example).

Next step- can financial grants improve the ecosystem? It is a complicated question to address universally. What are we trying to measure? Radiation Oncology has attempted to quantify outcomes (in contrast to other specialities), but we fall short of proposed QUANTEC criteria. Besides, each institution follows specific fractionation that makes it difficult to compare results from a broad spectrum. My point here is that unless we have a quantifiable system in place that measures quantitative outcomes- we will sputter along with fanciful techniques and hair-splitting instead of a genuine advance in cancer therapeutics.

This is also instructive:

VC-backed startups connect the chasm between university science and corporate invention. VC managers often hold advanced degrees in the subject matter they invest in, and accumulate commercialization experience over their careers. Startups also do not have established business models, calcified over time, that make established firms resistant to disruptive ideas. Research from Xerox PARC, for instance, was commercialized successfully by Xerox only when it connected to the core business of the firm (e.g. laser printers), but not when it diverged from it (e.g. GUI, ethernet).

Yet, VC has not been a perfect solution, as investments have mostly been concentrated in the life sciences and digital innovation. According to data from PwC Moneytree, information and communication technologies (ICT) and life-science startups received around 83% of all VC investments between 1995 and 2019. This means that very little funding is going to innovation in other sectors vital to advanced economies, such as energy, which relies on fundamental advances in material sciences and nanotechnology to deliver more efficient grids and safer power generation.

Sadly, it is the likes of WeWork and Uber that gets the attention. A fraction of 100 billion USD from SoftBank can spur on quantifiable research. Yet, it continues to battle in fintech space, and the brightest minds in the world are fixated on creating the next TikTok. None of the VC’s in India, for example, understands the healthcare space but instead investing in creating a network-effect.

Likewise, we also need to understand the value of research getting out of the established scientific institutions. Have we, in India, innovated in Tuberculosis medications? The Directly Observed Short Course Therapy (DOTS) was an Indian innovation, but we instead allowed it to reimported under the aegis of the World Health Organisation. We haven’t created a cure for Malaria or found a specific methodology for combating childhood parasitic infestations. Parasitology continues to draw inspiration from the research work done in the 1940s with outdated medications from the WWII era. Yes, it is that old.

Here’s another blurb that is very pertinent:

Technical uncertaintyis, put simply, whether a given technical problem can be solved using a proposed approach. Commercial risk refers to the challenges of accurately assessing demand for a proposed product and the likely costs of scaling up and servicing the market. Most software projects have limited technical risks: the key question there is what should be done, rather than how it is to be accomplished. Commercial risk is managed by setting out commercial milestones (such as number of users, or cost of customer acquisition). As the startup passes a milestone, it gets additional investment to move forward toward the next milestone. The life sciences face significant technical uncertainty, but market uncertainty is very low, since the need for new medical treatments and devices is relatively stable. Projects in life sciences can also be mapped to specific milestones and managed accordingly. As a project successfully achieves a milestone, investors can estimate the gain in value based on the likely size of the market.

This, of course, misses out the key fact- Angel investors bet on the commercialisation, and the other players come in to fund the network effect. For example, a prominent VC could only fund a system of “yellow pages” for doctors. It is hailed as a “success”!

Therefore, a progressive set of ideas need to be instituted to see the practical application. I was an attendee in a prominent International conference (I had won a travel grant for my mobile app) and was attending a startup pitch for research grants. Unsurprisingly, the host institution won the grant for something that was already well known. Perhaps there are other factors in play or those awarding the grants feel comfortable with they are aware of.

Specific bridge programs exist to address this yawning gap of applicable research. In India, we call this as the “jugaad”, and I think it refers to the ultimate innovation- creativity with the existing solutions to build something completely new. We haven’t learnt from these real-life examples to scale them up commercially.

The cancer innovation engine has definitely slowed down (in retrospect), and the only way to address this is to apply existing technologies- radiation therapy, more effectively. Chemotherapy is only an adjunct and definitely not the “cure”.