What’s your “Thing”?

September 18, 2020

What is it? Hard to know. At first, it seems vague. Perhaps just a feeling. Too far away to see, touch, or smell. But we know it exists. Or at least it could. Certainly, a possibility.

But what would it take, to clarify, to bring within range? How might it sound, to give it a name?  To define the elements that make it real. Bringing something to life and adding it to our own. 

An aspiration unearthed. Unpacked from our long list of wishes. Sorted and resorted to pick just the one. Adding in the specificity to give it form. Something that we begin to see and get to know. A new companion per se that gives us what we need to feel. A sense of purpose, of progress. A challenge worth taking; as we give to it what is reciprocally due. 

Would evoke responsibility if, we, were to name it. No turning back, once a creation is created. Certain to bring us pride. Yet never too far from worry – how would it all turn out? Only a journey together would tell. 

Why, would we do it? Take such a gamble. Aren’t times hard enough? Easier, perhaps to just endure. Take what is given and accept what we’ve been told. “Ride in the tide”, chose no destination.

Or for exactly those reasons, we reject how “things” are. And because it matters to us and perhaps to others — we decide to put a name on a “thing” that we will put it into lives, add it to our days and weeks ahead. It will be part of the history we make. The life we enrich. And the pride we restore.

2020 will be our platform. 2020 will be a year in which we will rewrite the rules by which we live and in so doing durably etch our new world. Capturing our words that clarify. Picking the words that define. Underlining the words that lead to our actions. Standing on the words that inspire. Finding and fulfilling our superpowers.

The summer is behind us, we now begin the journey toward a better 2020. Focused on just OneAmazingThing, at a time.

Join us.


One — AmazingThing

June 23, 2020

Amongst all, we are the only numerate species.  Numbers move us. They give us scale, time, proportion, price. The only thing that this is both endlessly large, and never endingly small. To master them is to fly. Yet in all, they evoke fear. Our apex invention, and as their creator we now cluster, and cower, amongst them.

“Top ten” lessons of love, life, happiness, and all else are irresistibly consumed. Rankings, percentages, probabilities, each give us a sense of place and prediction. The perception of power – the feeling of control. With numbers, we confirm our status and reinforce our security.

If we avoid the decimal and remain positive, our first stop from “nothing” to “something” has to be the number “one”.  Even though it is just the beginning, “one” can be huge. And often seems to be too much. That first step. The decision to act. To just begin.

Yet it is its simplicity, that makes “one” is a superpower.  By focusing on just “one”, we can clearly define what is needed. We can affirm the timing. Make the commitment. Check the box. Get it done.

2020 will be our platform. 2020 will be a year in which we will rewrite the rules by which we live and in so doing durably etch our new world. Capturing our words that clarify. Picking the words that define. Underlining the words that lead to our actions. Standing on the words that inspire.

Come July, we begin the journey. Focused on just OneAmazingThing, at a time.

And “after talk”… “we walk”, together.

Join us.



June 11, 2020

On one thing the whole world agrees — these are “amazing” times … yet not impressive. Hardship, sadness, loss. Fear of the microscopic and fear of the systemic. Jobs untethered to place and many simply erased. Schools not in “lock-down” but in “locked-out”. Long term inequities and injustice re-unveiled and dripping from society’s brow.

Emotions evoked that quicken our pulse, lessen our sleep. Defying description but needing to be understood, to be explained. A moment that begs for leadership, for gratitude, for empathy. Yet most are out of stock.

Our thoughts are framed with words. From these, we gather our resolve. Chart our action. Restore our autonomy. Our words provide the mental bread-crumbs, not only of our journey and history but also to a true north leading us back to our intentions when we wander. Our words are our mantra on which we take action. The shared language under which we affiliate with others. They speak to our passion. They define what we believe and what we abhor.

Regardless of all, 2020 will be our platform. 2020 will be a year in which we will rewrite the rules by which we live and in so doing durably etch our new world. Capturing our words that clarify. Picking the words that define. Underlining the words that lead to our actions. Standing on the words that inspire.

Come July, we begin the journey. Focused on just OneAmazingThing, at a time.

And “after talk”… “we walk”, together.

Join us.


Too High?

January 23, 2020


The Fall of Icarus — Gowy, Jacob Peeter (1615–1661)

Too High?

As an earth-bound species, our fascination “to be above it all” — to transcend, to soar or to approach the divine — is timeless. The Egyptians, Romans, Greeks, Chinese, Indians, and peoples all across time, have ascribed flight to their deities and embedded flight into their fables and legends retold. To fly was the ultimate expression of power — be it a dragon or one of the yantras detailed in ancient Sanskrit text. To fly was to inspire awe.

But no legends of flight have endured like the story of Icarus, son of Daedalus. As first mentioned by Homer, Daedalus was a mythological sage and egotistical innovator. Credited with the first bathhouses, dance floors and the most life-like sculptures of Athens. Yet in a fit of jealousy, the accomplished Daedalus killed his ascendant nephew and was banished from Athens to Crete. There he built the inescapable minotaur’s labyrinth for King Minos but, as punishment for conspiring with the Minos’ lustful wife, he was sentenced to be forever imprisoned atop one of the island’s highest towers with Icarus, his only son.

While wishfully imagining their escape, Daedalus envisioned a human-sized wing that could be assembled from the dropped feathers of his avian companions. Attached only by thread and wax, Daedalus implored his son to take “the middle way — not to fly too close to the ocean waves nor too close to the intense heat of the Aegean sun.” Daedalus watched in dread as Icarus could not bring himself to heed his father’s warnings — soaring higher and higher until it was too late. A trip “too high” had claimed another.

Surely inspired by these myths and more, human aviators have moved beyond copycat bird wings to eventually harness the buoyancy of lighter than atmospheric gases (at first hydrogen and then helium). In these so-called “balloons” we have soared to life-threatening heights. As one of the world’s longest still standing records, in September 1862, James Glaisher and Henry Coxwell ascended to ~37K feet without the aid of supplemental oxygen. Amazingly, both Coxwell and Glaisher survived thanks to some last-minute luck. As they rose to nearly seven miles high, the temperature dropped well below zero and they began to notice difficulties with vision. “I could not see the fine column of mercury in the wet-bulb thermometer, nor the hands of the watch, nor the fine divisions on any instrument.” While Coxwell climbed out of the basket to free an entangled gas release valve, Glaisher was already losing consciousness.

At the time, neither Glaisher nor Coxwell could have understood the cause of their “balloon illness” that was brought on by the extreme cold and scarcity of oxygen. They may have also suffered from the “bends” as a result of the swiftly falling pressure during their too rapid ascent. The net result was nausea, paralysis and eventually total loss of consciousness.

Since these bold or perhaps foolish ascents, humans have conquered increasingly dizzying heights, but most with the advent of portable oxygen. The current record for a round-trip balloon ascent is 69K feet; while others have used balloons as platforms for skydiving near the very edge of outer space at 128K feet. However, these oxygen-assisted endeavors blur the line of what humans can “personally” accomplish.

Our true limits are set by biology, not engineering. Since we have evolved to live within the specific confines of the earth’s atmosphere, we are keenly dependent on the 20.94% concentration of oxygen that is evenly distributed from pole-to-pole and from sea-level to the edge-of-space. Although the concentration of oxygen is the same everywhere on our planet, pressure and temperatures change dramatically as you go up in elevation and in response to local weather conditions. Per gas laws, this translates to the same percentages of oxygen but decreasingly fewer molecules of oxygen per unit volume as pressure decreases. And although lower temperatures will increase the density of air and thus increase the number of molecules per unit volume, the dramatically lower pressures at higher elevations largely occludes the effect of the colder temperature.

The workhorse behind the scene of our gasping breath are small (~7 microns across) enucleated biconcave cells called erythrocytes (or red blood cells, “RBC”). The most prevalent cell in our blood (and body) representing 25% of all our cells. RBCs are generated within our bone marrow, and upon maturation, live approximately 120 days in circulation. Within each RBC are ~300 million molecules of a specialized gas transportation protein called hemoglobin. Upon traveling through the oxygen-rich capillaries of our just filled lungs, each hemoglobin can bind up to four atoms of oxygen. Then, as RBCs traverse the capillaries of our distinct tissues, a lower dissolved oxygen level prompts the hemoglobulin bound oxygen to release. The free atom (actually a pair of atoms) “O2” is then rapidly whisked into cells for their acute use by mitochondria in aerobic respiration (i.e. making energy). Interestingly, RBCs themselves do not use oxygen but as an exemplary act of “cellular selflessness,” they rely on the less efficient anaerobic metabolic pathways to produce the energy they need.

At sea level or generally below 5,000 feet, all goes well. But as we ascend, the pressure swiftly drops and with it the number of oxygen molecules available per breath. As an example, the average atmospheric pressure is 29.92 inches of Hg at sea level, but only 8.45 inches of Hg at the summit of Mt. Everest (29,035 ft.). As the density of inhaled oxygen declines, our bodies promptly sense the changes and trigger the production of more RBCs. But the process of making more RBCs takes time, and beyond just increasing RBC numbers, our physiology requires several other metabolic tweaks to function efficiently at these higher elevations. Our lungs require an increase in hydration to support the more difficult gas exchange processes; thus our fluid intake requirement increases dramatically. As our blood thickens (polycythemia) due to higher cellularity, i.e., more RBCs, our cardiovascular system has to work faster and at higher steady-state blood pressures.

For those attempting new heights on foot, a slow process of acclimatization is effective in enabling us to adjust to the new conditions, while minimizing the effect (or risk) of acute mountain sickness (AMS). For those that ascend rapidly by balloon, helicopter or as a wheel-well stowaway, their experience is all too often grim. By the time one has risen from sea level to just 14K feet, the percentage of fully oxygenated hemoglobin molecules within each RBC has already dropped by ~10%. For those who rapidly ascend to just 17K feet, greater than 50% will experience AMS and run the risk of pulmonary or cerebral swelling (edema). Of the 110 known aircraft wheel-well stowaways (tracked in the US), over 75% have died. Of those that have survived, some traveling up to 39K feet and into temperatures as low as -81 degrees F, a rapid state of unconsciousness and the extreme cold likely enabled their survival.

Having recently awoken from being face down unconscious at ~20K feet in the icy cold rock scree on a steep Andean mountainside, I am reminded of the stoic words of Glaisher, the balloonist world record holder, “No inconvenience followed my insensibility.”

Yet perhaps more applicable was the flight of Icarus, as fate and foot had enabled it, “to be just one step higher, and then higher, had proven to be irresistible.”

A Forward-Looking Statement

January 12, 2019

Talking about the future with assurance takes faith. For those in a business setting it is often preceded with carefully crafted legalese, so-called safe harbor or forward-looking statements, that seek to come clean on just how uncertain, about the future, we truly are. Yet a future unimagined is a future unrealized. It is our power to predict, or at least the desire to do so, that sets humans apart.

A collective peek into the future of healthcare is attempted each year at the JP Morgan (JPM) Conference and this year’s January gathering was no different. Apropos to the fragility of predictions, it (thankfully) rained much less than had been forecast. None the less, all the conventionally well-prepared biotech executives had their, just in case, umbrellas at the ready.

This year at JPM I had the privilege to guide a discussion at the WuXi Global Healthcare Conference (v-restream begins at 148 minutes) on the role that advanced artificial intelligence (AI) and machine learning (ML) are hoping to play in healthcare. It was fascinating.

The conference had begun with R&D leaders expressing fundamental concerns about the implied limits, derived from algorithm training bias, of AI/ML in Rx discovery. To unpack this in greater detail our conversation focused initially on the key raw material “data”. Swiftly moving beyond the generalities of “big data”, into a focused discussion on what is commonly missing in opportunistic datasets. On the fact, that all too often the “available big data” are neither of sufficient quality nor in an optimal format to generate insightful AI or ML derived observations – and how when we elect to make data compromises we do so at great risk. Because the same supra-human abilities which enable AI/ML algorithms to detect subtle signal in large multi-dimensional datasets makes them equally (and hauntingly) good at detecting, then erroneously focusing on, artifactual noise.

Even in relatively mature fields, like population genomics, we are only just beginning to collect the right data needed to enable scaled AI/ML derived insights. The same for preclinical, clinical and even behavioral data. Building scale, quality, and continuity between carefully collected datasets has essentially just begun.

In addition to recent attention on improved data collection, rapid progress is just beginning on the analytical side. Some of which are derived from customized hardware that process image-based data with greater and greater ease. Software and algorithms, particularly in deep learning approaches, are now progressing rapidly too – with new benchmarks being eclipsed daily.

Yet the raison d’etre of the session was on value creation. On the possibility that AI/ML applications could enable smarter drug development, perhaps making R&D processes faster or cheaper and on ways in which real-world evidence could cross-correlate additional behavioral, contextual, and treatment-related insights – collectively leading to even more value-advantaged medical solutions.

Yet, our starting point is somewhat grim. Even after decades of trying (without any AI/ML help), we have little to demonstrate that developing innovative medical solutions is getting any faster nor have we reduced our rate of failure. In fact, the data would suggest, that on an ROI basis, as an industry, we are getting swiftly worse.

Can these AI/ML tools help? It is too early to be certain, but the trends are encouraging. As with many new tools, much trial and error await. Some will seek to use these methods with the wrong data and follow inferred fantasies to false lands. Others will seek to use them in model settings for which we have insufficient correlation and causation linkage. But transformative progress seems inevitable. Using built-for-purpose datasets, filling the air gaps between those data to facilitate longitudinal forecasting, then integrating -omics, personal context, and individual behavior data with long term intervention or prevention settings are when and where the first big contributions await. The ability to eliminate costs (and steps) associated with “business as usual”, will require not just technology advances but ecosystem changes involving regulators, policy, etc. But these too are likely as more and more evidence of value accrues from platforms built on sound datasets and validat(able) models.

Predicting the future is a fool’s bargain. But with some assurance (i.e. faith), one has to imagine that the healthcare contributions of AI and ML will (eventually) be material. And beyond a blind faith in technology, we will need equal attention on insightful ethics, regulation, and policy. Data ownership, dynamic consent, privacy, security, and data use remuneration all will prove to be as central as any chipset or AL/ML algorithm. For the world that we seek to serve, will expect that our industry understands their needs and personally defined interests.  This near-future will demand that we earn, honor and respect the profound trust bestowed on those who work with the personal health and wellness data-diaries of the world. This is a setting in which the Hippocratic oath primum non nocere (first, do no harm) must always remain front and center.

JPM at 20

January 6, 2019

Habits are useful things. Behavioral patterns that are etched into our brains and upon which we rely; they are the autopilots of our lives. Habits increase the efficiency of our mind, freeing up the neural bandwidth needed to capture and process the new. For many of us, heading off to Union Square in early January is a deeply embedded ritual. A habit that has become as mindless as tying our shoes.

For those arriving from a distance, JPM will include a flight filled with well-known faces. Those for whom San Francisco is home will experience a temporary invasion of overdressed, swift footed, wing-tipped (or some, but still way too few high-heeled) biotech immigrants. A flash mob that will bring with them commensurate surge pricing on everything imaginable. While this January habit simplifies our preparation, with its ease, in seeps complacency. Expectations of the similar narrow our mental aperture and bring with them the risk of overlooking the new.

As we gather our things, board our planes, trains and surge priced Ubers to rejoin as a community for the 37th J.P. Morgan 2019 Healthcare Conference, this year could be one to reboot our expectations: to discard a little of the known and in so doing make space for the unexpected.

Over the last several Decembers, I’ve habitually reminded myself of key milestones that the biotech industry has traversed since the first JPM or, as it was previously known, H&Q. Perhaps you will also find these historical stepping stones intriguing.

JPM at the beginning

JPM at 5

JPM at 10

JPM at 15

This year our Flashback takes us to 2001, when the conference would reconvene for its 20th consecutive year. 2001 was to be the second year of the new millennium: a year that had moved past the threatened calamities of the Y2K “divide by zero disaster” but not the dot.com bubble that had preceded it. 2000 was the year that ended the first irrational chapter of internet/tech investing, washing way billions of dollars invested dot.com businesses. Biotech had ridden this market wave as well, ending 2000 with the largest number of biotech IPOs (56), breaking the previous record of 47 in 1996. By the end of 2001, only six new biotech companies had found a home on public markets. Independent of this market malaise, several new transformative medicines were approved in 2001 such as Gleevec (approved in just 2 months by the FDA), Remicade, Tenofovir, all three of which remain mainstay treatments today. Science charged on as well. Just eleven years after its start, and 4 years before the originally stated completion date, the first draft human genome sequence was released in dual publications, one in Nature from the 20 institutions publicly funded consortium led by Eric Lander alongside one in Science generated by the for-profit team led by Craig Venter’s Celera Genomics.

Only during a few days of our lives do we witness the historical. These days we vividly remember where we were, who we were with, and maybe even how we were dressed. In 2001, one such day began for my team with an early breakfast. At a hotel in San Francisco, with investment bankers we watched in shock as United Airlines Flight 11 plunged into the World Trade Center north tower. Seventeen minutes later, with black smoke billowing from the first impact, UA 175 vanished into the sister tower. About 50 minutes later the second tower to be hit collapsed, followed soon by the other. More than 3,200 innocent lives were lost. A black swan day that completely overturned our agenda. Those meetings, nor the subsequent offering would ever happen. Carefully planned business milestones were rightly overshadowed by the tragic loss of life. Short on cash in a paralyzed market, we pivoted and sold that company to another in need of late-stage assets. Lesson learned and memories etched, the team moved on.

But even before the fateful events of 9/11, the most serious global economic slowdown in 20 years had begun. The U.S. economy had entered into a recession, sending the European Union into a sharp economic contraction. The Asian economy, which had been slowly recovering from the 1996 financial crisis, also slowed its pace of growth. The Latin American economy was staggering with political disturbances beginning in Argentina. The world and its markets seemed fragile and rightly so – as true then as it is today.

So, as we head off to JPM, let’s reflect on the year just completed. In 2018, over 70 biotech companies have gone public on global exchanges, raising a cumulative $8.3 billion. This eclipses the previous peak in 2014, during which 88 biotechs raised $6.3 billion in IPOs. On average, 2018’s biotech IPOs each raised more than $116 million, with a median raise of $98 million. In 2014, those figures were $73 and $58 million, respectively. According to R.W. Baird, biotech investors also poured $23 billion into 210 follow-on offerings during the first 11 months of 2018. That said, 30 of the US-based 2018 IPO class are now trading below their opening price and the NASDAQ Biotechnology Index ended the year with a loss of 14%. iShares Nasdaq Biotechnology ETF, which is benchmarked to the NBI, ended at a loss of 13%. These numbers stand in context to the broader markets where the Dow Jones Industrial Average lost 7.1%, the S&P 500 shed 4.5% (including dividends), and the NASDAQ Composite ended down 4.8%.

Back in healthcare, 59 new medicines were approved by the FDA this year, compared to 46, 22, 45 in 2017, 2016 and 2015 respectively. These 2018 approvals are an impressive collection of novel and some perhaps even curative treatments. As an industry, we have much to be proud of in 2018, yet much left to do.

In now what has become perhaps the most impressive JPM habit, our industry’s innovators are certain again this year to report on even more stunning advances. New treatments for diseases for which not long ago patients had no hope. Yet we must aspire for more. We must embrace the increasingly grave diagnosis of the global healthcare system itself. The innovations we invent save lives. Yet they are extremely expensive to create. Their resulting price must both sustainably support the required investment as well as be linked to the validated value to the patients they have helped. As we have tirelessly worked to serve those with medical needs, we must now double down to reinvent the healthcare system on which we all equally depend. Bringing similar ingenuity to the table to more effectively demonstrate the utility and value of the solutions we provide.

See you there, and bring an umbrella!

2018 – “Thrilling Three”

December 21, 2018

2018 will be recorded as the year of “Us and Them” – a textbook illustration of how fear triggers us to cluster.  To partition with the familiar. To seek strength amongst tribe. To emphasize boundaries and seek specificity in who “we are”, while seeking to distance (or protect ourselves) from who “we, are not”.

Fear is powerful and useful. It reminds us of the fragility on which health, peace, and prosperity rest – it heightens the pulse, sharpens our attention, prepares us to react. On fear, we have long relied. Yet in exchange for enabling our readiness, fear must short-circuit our analysis. It removes the time to consider, the chance to challenge the facts and the opportunity to double check our assumptions. Fear’s primary utility is transient and when run on overtime, one must, in Franklin D, Roosevelt’s prescient 1933 inaugural words “must begin to fear, fear itself”.

This year the fear of being left behind, or worse, has triggered populism across the world. Most recently have been our “yellow jackets” of France. Just before it was Bolsonaro winning on the promise to put “Brazil before everything, and God above all”. Or Mexico’s completely new political MORENA party and the resulting presidential win of AMLO. A direct response to the grisly fact that 25,000 Mexicans were murdered in 2017— the highest number ever recorded.  With an estimated 130 political Mexican candidates and other public officials assassinated just during the 2018 election alone. Prior to these we had the 2016 US election and followed just after by Brexit. Both catalyzed by “us vs. them” thinking.

Markets react to fear in humanly ways as well, with rapid reflexes that shift portfolios from risk to value. And as we near the end of 2018 we’ve seen tremendous shifts in market perception along these lines. At the governmental level have been tariffs, the economic equivalent of immigration controls. The US has a long and storied relationship with fear inspired trade policy. In fact, the second bill of the newly elected George Washington was the Tariff Act which imposed strict (and steep up to 60% for silk) tariffs on all incoming products into the fledgling country. Said to be intended, to help pay down the war debt, it was also purely protectionist, as Hamilton was fond of quoting, “this Act is critical to protect our infant industries”. The “we” in this instance was clearly the young and comparably inferior US manufactures and the “them” the sophisticated British industrial complex.

But where does this take us?  It helps to start with evidence. To look for demonstration and to look at what we know to be true, while avoiding the natural reflex to imagine the negative.  To seek and see the positive. Each year I collate and select out three remarkable new innovations that have caught my attention and prompted me to say “wow” that might change everything. These I call my “thrilling three”:

2017, 2016, 2015, 2014

As a reminder in 2017, it was MoBikea rapidly expanding ridesharing platform that a built customer base of over 200 million who averaged of about 30 million (peddling!) trips per day on a fleet of eight million bikes across the world. The equivalent of taking 1.24 million cars off the road for a full year. One year later, the shared-bike trend continues to rapidly expand with new formats like scooters (see below) and an increasing use of environmentally friendly electrification. Next up was WeDoctor, a Tencent Holdings-backed online appointment booking, prescription, diagnosis and payment service. By end of 2017, the company already had 150 million registered users across China. Using their mobile platform, users could both find the most appropriate doctor to handle their needs but also secure an appointment, have immediate access to their medical test results and pay for their services – all from their mobile phone and without the conventional hours of queueing. One year later, telemedicine continues to sweep across the world and will soon to be seen as conventional and “old school” as the home visit. Lastly was Mitobridge – a biotech working on medical conditions that result from inborn errors in mitochondria function as well as looking to find methods to maintain mitochondrial fitness in settings associated with aging, inflammation and the host of conditions that result from cellular atrophy. By January of this year, the Mitobridge had been acquired by Astellas Pharma to help further expedite the advance of these technologies and the “primordial pool” of mitochondrially focused companies continues to grow.

So, for 2018 here they are:

Microbility – We tend to like things to be “in their place”.  We have bright lined parking spots to make sure our cars are tucked in neatly, we have drawers for our folded clothes, and tidily named file folders to keep all things organized (except for that desktop!).  So when we see what seems to be the random array of shared bikes left as is, unowned or unchained, it stirs us up. Yet, behind what might seem to be all the sidewalk clutter, lies one of the most useful new solutions for urban gridlock (and all the resulting CO2 belched by those frustrated drivers) – single person electric transportation.  Nothing beats the dual benefits (health and climate) of a self-propelled bicycle, but they not for all and certainly take much larger footprints on the sidewalk (or parked in the office/home). Then there is the remarkable energy savings and the calculus is simple.  Transportation of anything is all about weight. Given their form factor advantage, e-scooters are highly efficient. By way of example, a typical gasoline-powered car (~4,100 lbs) can travel a little less than a mile on one kilowatt of energy. With the increased efficiency of a typical electric car (e.g. Tesla or Volt) one can travel about four miles on the same amount of energy.  Whereas on an e-scooter that same one kilowatt can buy you more than 80 miles of transport.  Hope to see you, next to me, scooting past that traffic jam soon!

Democracy – In 2018, we have begun to fully grasp the extent to which electronic meddling has become commonplace in elections across the world. And although the format (memes, fake news, alias accounts, etc….) may seem to be new entrants into politics, the tools of propaganda, misinformation and societal manipulation have been commonplace since the invent of elections themselves. What is new, is the scale, potency and cross-border reach that these new e-formats can achieve. And in the yin and yang of all things, technology may have just the counterpoint needed to help re-invigorate our democratic muscles. For democracy to function, participants must believe that their vote matters – democracy relies on engagement. Few things pull us forward more than peer-pressure, and in voting too. Emotions were unusually high for the US 2018 mid-term elections, and mid-term voter turnout was the highest in a century. Aside from emotion, it appears that many where pulled into action by get-the-vote-out tools that allowed individuals to target their contacts with SMS messages that were synced with voter registration databases.  When it comes to voting (and democracy!) it is critical that we maintain interest, even if it takes some technology to “guilt trip us” into caring.

China 1st – While participating in a keynote panel at the 2015 Shanghai DIA Annual Meeting I was asked: “what would be the most meaningful signal that China’s pharmaceutical markets have come of age”. My answer was simple, “when the first/best-in-class drugs are approved – first – in China”, approved here before other regulatory approvals, eg. FDA, EMEA etc.. This will signal that a new dawn has arrived for all of China’s patients awaiting access to the world’s most innovative medicines”.  Just three years later, that day has arrived.  Just this month, China has for the first time approved a treatment from a global drugmaker before any other market, illustrating its recent push to bring in cutting-edge medicines. The product is called “roxadustat”, a new anemia drug from AstraZeneca and Fibrogen.  And this Chinese approval is well ahead of the potential approvals in the other markets. Since 2015, profound change has occurred within China’s regulatory body, the “CFDA” and the roxadustat approval is just one of the many of the fast-moving outcomes that will soon become more and more evident as China’s healthcare presence ascends. Approval is one thing, pricing is another – another critical innovation topic that I have covered a lot this year but will leave further wishful thinking on this one to another day.

He Did It – As “thrilling” as these 2018 stories are, one would be remiss not to mention in, an end of year recap, the “chilling” (if not worse) advances reported in gene editing.  The revolution of evolution represented by gene editing has been reflected on here before. For all its potential, the world’s best minds had made it abundantly clear, “we are not ready to move beyond experimentation, into clinical exploration”. The risks are simply still way too high. The lists of technical (and ethical) concerns still way too long (off-target effects, the likelihood of mosaicism, etc.), the need for explicit unmet medical need/urgency before any clinical attempts could ever be considered. And the absolute need for complete transparency and robust oversight. For reasons yet to be understood, a Chinese researcher, Dr. He Jiankui, appears to have breached the collective trust.  To have inappropriately enlisted participants (disparate-to-be parents) and created the world’s very first genetically engineered twins. Presenting to a stunned group in Hong Kong, He nervously sprinted through his data. Full analysis awaits, but if confirmed the results are at a minimum deeply saddening. With hope and grace, the young twin girls (Lula and Nana) will suffer no long-term medical hardship, but only time will tell. But what must result is a deeper resolve to hold those who exploit the “possibilities” of these technologies accountable until it is abundantly clear how best to ensure they are most effectively and appropriately used. For the privilege and trust bestowed on those trained with these skill sets, they must be expected to understand the resulting responsibilities.

Truly yet another “historic” yet “thrilling (and somewhat chilling)” year. Next up, J.P. Morgan 2019 and reflections on the historical path on which our healthcare innovations have traveled to get us here.

And Happy Holidays to all.

“Come on dowwwwwn!”; fateful words that all anxiously await.  Having pinned their hopes on being plucked from the live audience for “Contestant Row.” The first step from which they might win a treasure trove of goodies, based on their uncanny ability (or luck) in guessing prices – prices of products that can range from a can of mushroom soup to a new car or a dream vacation.

“The Price is Right” game show has set countless records.  It is the longest-running network television program in history (currently in its 46th year).  And even today it remains the #1 watched USA daytime television program.  Although it has tweaked its games and products slightly (adding items like VR goggles alongside the soup) to remain relevant across the decades, the vast majority of its fast-paced format remain wholly unchanged over all these years.

Game experts suggest that it is the “high win-per-minute ratio” along with the “use of life skills” (i.e. accumulated knowledge derived from purchasing) that are the key ingredients in the game’s attraction.  But when asked why, Bob Barker the host of the program for 35 years, made it clear, “The reason it was so popular originally and why it is still popular is because of the powerful basic premise of the show… everyone identifies with prices. The minute we put something up for bid and a contestant offers a price, all of us are deeply involved.”

Books are written and websites filled with stories of, and tactics for, winning (with all the resulting statistics).  Some of “The Price is Right” gurus will push for product pricing memorization drills and card counting-like training.  Others will drive you toward a game theory-based approach which focuses more on the optimal counter bids than it does on knowing the price per se.  For example, from Contestants Row, if you are last, then bidding either $1 above the lower bidder or $1 above the higher bidder, depending on the spread between the other bids, results in a 54% winning outcome as compared to 34% for all other strategies.  And for the other ~75 sub-games, similar tactics abound.

But the apex moment of the show is the “Final Showcase”; here is where the big-ticket items await and only two contestants make it to this stage. The showcase offerings are presented as bundled packages.  Often with a theme, but in each instance, each contestant will need to put a total price on one or the other package.   And as with all The Price is Right sub-games, it is critical to get as close to the actual price as possible, but to NEVER OVERPAY; for being even $1 over is an automatic losing bid.

Interwoven with the psychology and success of The Price is Right are keen insights into human behavior and motivation.  As highlighted by Barker, we all care deeply about price.  And although we may differ in what we believe is an appropriate or “fair” price, we have visceral reactions when we believe we may have overpaid. The positive aspects of getting a good deal are important and motivational too.  We will drive a great distance, sit in a cold pre-dawn Black Friday queue or perhaps even endure the tedium of cutting coupons to save just a little money. But as rewarding as it feels to save some, we have significantly more potent emotions attached to losing money.  And The Price is Right wonderfully highlights this with its overbid elimination rule.  We always feel, if/when we have overpaid, that we have lost – we feel cheated, or worse, we feel stupid.

For the vast majority of our transactional lives, we have agency, experience and expertise in buying stuff – in all but one. When it comes to buying the products and services on which we will all eventually seek and need–namely healthcare–we must all blissfully proclaim utter ignorance.  For when it comes to these matters, we’ve been trained to presume that “price” cannot matter.  Yet matter it must – any illusion to the contrary is truly a fool’s folly.

But what price is right?  Who should decide? What value has been received? How can we know?  These are but a few of the thorns in the briar patch of health economics.  And depending on who you ask, the answers vary wildly.   Ask the parent of a critically ill child and even the mention of price can evoke condemnation – “how could you?!!”.  A similar query to a physician will often result in questions regarding the “how could we know;” medical outcomes come in variation, often wax and wane and each are steeped in long-term uncertainty; “this is more of an art than a science.”  Ask an Rx R&D executive and they quickly retort, “be careful, if the incentive to invest in the remarkably risky business of drug development is compromised, then medical innovation itself will die a swift death.”  Or speak to a payor and the conversation quickly turns to prevalence and value.  In the setting of a single payor system, the conversation hinges less on time-to-efficacy and more on population coverage cost; a calculus of can they, the actuarial pool, truly afford it.  In the US, in which coverage responsibility jumps fleetingly with each change of employment, any conversation of long-term savings/value with payors generally falls on deaf ears.  Their businesses are living in the moment; what claims will we have to pay this year.

But regardless of these complexities and headwinds, we must pave new ways.  Develop new systems in which the vagaries of treatment effect can be more effectively classified, if not truly quantified. Build new business models and relationships with those who seek treatment, allowing them to actively capture the data on which their benefits can be more clearly understood. This real-world data must be entirely owned by them, used per (and only with) their agreement and their participation should be economically (and attractively) rewarded.

To move toward a world in which costs (i.e. prices) are clearly understood by both the recipient (and really the buyer) and those that provide care, the real cost/price must enter into the picture. In this new landscape, deeper patient engagement becomes expected and incented.  It requires an utter commitment to personal privacy; underwritten by sound policy/data security and is as focused on the long-term as it is on near-term outcomes.

We have a long and difficult way to go.  Today, we see steady annual increases in Rx prices, without any commensurate proof of increased cost or utility.   While global sales of branded drugs rose from $720 B to just under $800 B between 2011 and 2017, the volume of prescriptions filled concurrently drop from ~998K to 584K. Over the same time window the average of branded Rx prices increased between 6.5-14.0%.  For the top 45 already approved branded drugs, annual price increases drove >60% of the 28% US sales growth between 2014-2017.   Innovation is remarkably expensive, particularly in the setting of new Rx treatments. Further, it is certainly true that of every healthcare dollar spent, less than 25 cents of it is spent on drugs.   But that said, when buying “stuff” as opposed to “services,” per unit prices are particularly sensitive and increasing prices well above the rate of inflation is even more so.

Just imagine a day on which informed patients, rather than hyperbolic contestants, were invited to “come on dowwwwwn” and take a seat at the table of “The Price is Right for Healthcare” – we would begin to see a new dawn.   A day in which prices in healthcare are set exactly like they are in all other markets.  The right price based on the value thought to be received, by those who paid.  Some will be willing to pay more and others less.   Some will expect brand and others will look for savings, but all will be dramatically engaged in the process.  Prices will be dynamic, reflecting market-driven decisions and patients will have much more and tailored information to help support their purchasing choices.  Outcomes, or least prices, will come with guarantees.

Until patients help set prices and personally determine value, all too often they will feel cheated.  And the new tools on which this paradigm rests must be the responsibility of those who seek to enter this market.  If one cannot provide a means by which outcomes can be assessed, by the patient themselves, then they too will soon prove to be relics – the history of medicine is filled with them.   As the industry walks down the plank of year-over-year price increases, an abrupt end awaits and the waters below are not friendly.  Building robust evidence platforms to validate utility (value) and ensuring consumer-driven advocacy is the only “pricing lifeboat.”  We all want and will need, medical innovation, but the Price (must be) Right.

Image Source.  CBS.com


Birth Right or Right Birth?

October 29, 2018

From the hand of fate, we are all dealt our cards. To each, 23 chromosomal pairs – each one a blended representation of the genetic precedents that have preceded us. Outside of identical twins, no two chromosomes are ever the same and their sequence similarity to our forbearers diminishes rapidly with each iteration; i.e. next generational birth. By the time you have gotten to 10 generations back, there is only a 50:50 chance that you share any of a given ancestor’s DNA. This is to say, that our genes are not our genealogy. Yet we are still related, regardless of our germline.

Our human need for kinship runs deep. With those that we believe to share bloodline or tradition, we have banded for millennium. Together, we have suffered and shared in life’s hardships and spoils. When separated, we swiftly re-partition into the groups that we feel we belong. As humans, we deeply seek and need to be members of “our tribe”.

In cultures spread across time, “banishment” has been put above “death” as the-ultimate-punishment. If you broke with accepted traditions or appeared to reflect something too far afield from the “norm”, ex-communication was the group’s response.

First impressions are critical. Extraordinary effort is placed on distinctive dress to ensure one’s quick recognition amongst the tribe. Perhaps a specific type of feathers, jewelry, garment or graphic design. To belong was to be safe; as true then as it remains today. As time has passed, our history has ridden alongside us. Visual triggers remain a key way to reinforce our tribal clustering. Whether it is skin color, gender or any other physical feature that could be used to filter, identify and sort. Our legacy biological systems are built on these visual tools.

Yet we’ve begun the long journey “to see past what we see.” To notice the extraordinary similarity we share with those who may appear to look just a little different.  To realize that we so often share more in common with those whom we have shared aspirations but perhaps a different external wrapper. And to acknowledge that even with those that we seem to share little, we all share the same responsibilities. To respect (and harness) our differences, to expect shared resources and to demand just treatment and equal opportunity.

On the long journey we have seen many moments of remarkable advancement. Milestones in which freedom and equal rights have been extended to those for whom they had long been denied – providing more integration, then more evidence of our remarkable similarities and synergies. We find ourselves becoming increasingly comfortable with the expanded safety and productivity of our new empowered tribe.

Yet, habit is stubborn. New ways seldom run free from the past. When tired, worried or repressed, we cling to the old. Revert to reflex. Cower from the new.  Our slow advances on gender and race, get hip-checked as revelations on sexual exploitation (#metoo), or police brutality (#blacklivesmatter), starkly remind us of today’s residual societal asymmetries.

Similarly, our remarkable global progress on gay, same-sex marriage and gender rights become clouded by anti-scientific policy recommendations proposing that natal birth designation provide an irrevocable definition of gender. If enacted, this line of thinking would seriously reverse the rights for those in the transgender community – critical and current ballot box issues that would reverse the path of inclusion and return us to our dark history of narrow-minded banishment.

To be born is a miracle. For some a work of the divine and for all a demonstration of the pristine – to be human. Every birth a never before (or again) blend of history. A forward-looking statement derived from the trials and tribulations of every forbearer that precedes us. In some, we will seek to claim direct kinship or a shared bloodline. But with all, we have shared upside and obligation.

We each fulfill a space on a spectrum.  How we think, in whom and how we love will all be completely unique. The veneer of our surface belittles the richness of our core.  As individuals we can become exceptional but only as communities can we be unstoppable. This is our true birth-right, as is our right-to-vote; squander neither.

Humans often proclaim that “intelligence” is what sets our species apart – the ability to analyze, to imagine, to organize, to then cooperate and execute. A unique gift that enables us to be remarkable.

Monuments to humanity’s capability are sprinkled all across the world — early works are colossal demonstrations of ingenuity coupled with brute strength. Consider the statues of Easter Island, Rome’s Colosseum, Egyptian, and early American pyramids, or the Great Wall of China as examples, each demonstrating a singularly human ability (and need) to reshape our world and leave evidence of our presence.

And as time and talent has unfolded, the complexities of our contributions have advanced as well.

Just imagine Michelangelo toiling day after day, for three years, on a suspended ceiling scaffold to complete his Sistine Chapel masterpiece in fresco (an arduous painting technique that uses freshly mixed wet mortar). In his mind, he had assembled the nine-paneled piece that retells the book of Genesis. Then to return again 25 years later, to the same sacred chapel, the actual room from which all future Popes would be selected, to toil for another seven tireless years painting the massive Last Judgement. What drove him? Was it intelligence, or something more?

Or consider the four stoic faces of Mount Rushmore. Originally intended to feature celebrities of “the wild, wild west,” sculptor and principle engineer Gutzon Borglum would have no part of that ill-considered idea. His vision was to record “leadership greatness,” in massive stone. With congressional funding and President Calvin Coolidge’s personal endorsement in hand, Borglum and four hundred fearless souls dutifully chiseled 60-meter granite renderings of Presidents Washington, Jefferson, Lincoln, and Roosevelt as a timeless (and today yet again timely) reminder of how “great character” is core to “true greatness.” Mount Rushmore is an engineering and artistic marvel, but here, too, something more was required.

These, and countless other examples, are certainly demonstrations of human intelligence.

But intelligence relies on something else unique to humans. Excellence in analysis, imagination, organization, cooperation, and execution all have a shared co-dependent variable. They each deeply inter-depend on us — the actor, the agent, the painter, the human — to truly and deeply care. Each is pulled forward by a personal purpose. By our durable (and uniquely human) interest in the consequence. For when we care, remarkable things can happen, and when we don’t, they won’t.

Sadly, for one of the most consequential and economically critical topics in our lives, “healthcare,” it seems we don’t actually care. Or, we don’t care soon enough.

Why is that?

There are many, many reasons for this, but the major contributor has been the fact that caring about our health early just hasn’t mattered much. For most of us, it has not felt as though caring before we need to would have much consequence.

What could we have actually cared about?

Well, we could keep an eye on our weight and/or what we consume. Perhaps we could “count our steps” and try to be more active. We could make certain that our children were vaccinated in a timely and complete way. Or we might regularly get our annual check-up and our gender/age-appropriate recurring tests. With some attention, perhaps we could try to get enough sleep.

If you generally took good (enough) care of yourself, you would have nearly the same risk of getting a disease, as say, your neighbor. If either you or your neighbor were eventually (and inevitably) unlucky and converted from being “complacent” to becoming “a patient,” the doctors and insurance companies stood ready to jump into action.

This general maintenance is about as much “caring” as we do, and it has mostly worked — until now.

In the near future, the way we care for ourselves should change.

The first actionable item we must work on is reversing healthcare passivity. As it turns out, most diseases have long incubation periods. And for most of these diseases, when detected early, our ability to curatively treat them is much higher than when treatment begins after symptoms entrench – cancer perhaps being one of the best examples. Even many infections are more effectively treated when caught early.

At the individual level, “caring” about healthcare in the future is to participate in the collection (and pooling) of the data needed to understand and eventually detect diseases at their earliest stages. The types of data involved will be highly diverse and increasingly captured by lower and lower cost in-home systems. These will soon move beyond today’s conventional medical tests (e.g. genetics, blood test, imaging, and so on) to capture a larger swath of our real-time exposures and biological responses (e.g. consumption, voice, eyes, gait).

And for patients undergoing any active medical intervention, their ubiquitous participation will provide the dynamic real-world data sets required to continuously optimize care delivery and generate the evidence needed to confirm the economic efficacy within the lives of every customer.

Advances in collection technology will minimize the personal effort required to participate, but the healthcare data itself must be owned by the individual who will be compensated for its use.

The greatest of humanity’s achievements have been made possible not only by intelligence but by a collective resolve — a societal push to reshape our world.

Our shared need to travel, to power, to transact has enabled the extraordinary infrastructure of our roads, airports, electric grids, sewers, banking systems, weather forecasting, space exploration, the internet, all of which were made possible by our pooled resources, rigorous covenants of compliance, and defined economics for their use.

As humanity’s knowledge base accrued past what shared stories and local apprenticeships could teach, mandatory (and free) education for all children was swept across the world. Again, a human achievement made possible and underwritten by the collective.

Healthcare must escape the constraints and shared stories of our past.

The secrets that distinguish between health and disease are written within the daily biological transcripts of every human life. These crucial bits of information are largely lost today, but they await our capture, assimilation, integration, pooled use, and returned reward.

But first, we must “care” enough to enable and empower their collection. Second, we must robustly underwrite their security, ownership, and privacy. And lastly, we must fairly value and transact upon their pooled use.

Death and disease will not overlook us. But in a preemptive healthcare system of the near future in which the biology and experiences of all individuals are pooled, analyzed, and used to optimize the outcome of everyone, we can remove “the hand of fate from our shoulders” for a much longer fraction of our lives.

It all depends on us “caring” enough to share, and being intelligent enough to look past the past.

As Elie Wiesel teaches, “the opposite of love is not hate. It’s indifference”.