Disruptive Diagnostics and the Business of Science

Former UT professor Tom Kodadek returned to address the postdoctoral student association of the School of Biological Sciences on April 25. He met a full house of about 250. The title of his talk was “The Ups and Downs of Moving ‘Disruptive’ Diagnostic and Therapeutic Technology from the Lab to the Real World.”  Dr. Kodadek is now with the Scripps Research Institute, in Jupiter, Florida.  Originally funded by the NIH, his work is now marketed by OPKO Health, Inc., which found the angel funding he needed to bring his theories to realization.

He first identified the standard approach to any drug therapy:

1. Perform basic research on the disease mechanism,.

2. Identify molecules in the blood that are unique to that disease, or whose levels change drastically.

3. Develop a specific method to measure the level of that molecule in the blood.

4. Commercialize.

This fits our standard model for diagnosis.  The patient feels bad and goes to a doctor for treatment.  Tests are run.  A cause is hypothesized and treatments begin while the patient’s course is monitored.  The shortcomings with the standard approach begin with the fact that we have to wait until we feel bad to get a diagnosis.  Also, tests are heterogeneous: any symptom suggests many tests.

Dr. Thomas Kodadek (left) at the Reception.

 Kodadek then offered a better approach.  His theory is that antigens must exist before symptoms reach perceptible levels: you are sick before you have a fever. With pre-symptomatic screening we could monitor for any active disease in its early stage, before the symptoms appear.  His recommended course is to routinely monitor the levels of dozens of disease-specific antibodies as part of any periodic medical check-up.  

To achieve that, we need to develop a large, broad, and deep array of synthetic artificial molecules that act as antigen surrogates. This is possible through combinatorial chemistry.

He then rapidly outlined the some of the details of his methodology for the audience of post-doctoral biologists at the School of Biological Sciences before re-aligning his presentation to the business community. 

Having left the University of Texas, he thought that he was about to go to San Francisco to present his ideas to venture capitalists.  However, he first was invited to speak to a group at  the Scripps Research Institute.  Feeling somewhat challenged to be sharing the stage with six Nobel laureates, he thought that he handled it well.  After the talks, the president of Scripps, Dr. Richard Lerner, came up to him and graphically explained that he was about to get screwed. Dr. Lerner introduced him to Phil Frost of OPKO Health, Inc.

Opko had just suffered a failed third-stage test of a major product initiative.  Phil Frost had a company in need of new work.  Opko also acquired Cytochroma, Inc., a company with “a suite of products for treatment of secondary hyperparathyroidism and hyperphosphatemia in chronic kidney disease patients.”  Another Cytochroma product screens for vitamin D deficiency.  In fact, said Kodadek, we may find that we are in the midst of an epidemic and not know it because we only now are coming to understand the many functions of that essential nutrient.  

Opko is also pursuing a screen for neuromyelitis optica (NMO). NMO is marked by the presence of AQP4 (aquaporin 4) and anti-AQP4 antibodies. With Bindu L. Raveendra, Hao Wu, and others, Kodadek published “Discovery of Peptoid Ligands for Anti-Aquaporin 4 Antibodies,”in Chemistry and Biology, (vol 20:3; 21 March 2013, pp 351-359).  In the same issue, working with Yu Gao, Kodadek published “Synthesis and Screening of Stereochemically Diverse Combinatorial Libraries of Peptide Tertiary Amides,” (Pages 360-369). 

Tom Kodadek with his friends at the Reception

Dr. Thomas Kodadek closed by  summarizing his experiences. “Work on important projects, not widgets. Incubate for as long as possible in the university before taking your work to the market.  Angel investors are better than venture capitalists.  Focus early on the people you bring in to start the organization.”

Following the talk the School of Biological Sciences hosted a reception.  About 50 people attended.  I met old friends Maggie Bishop of the Austin Chamber of Commerce, Benjamin Grosse-Siestrup of Antimicrobial Test Laboratories and Ken Russell of Metabolic Therapy, as well as new acquaintances Dr. Gregory Daniel Frank of XBiotech, and Dr. Priya Sridharan of the UT department of Microbiology and Molecular Genetics, and neurobiologist Dr. Sangeetha Iyer. (Dr. Iyer and I actually crossed paths in 2012 during South by Southwest. I was flattered that she remembered me.)

  

Previously on Necessary Facts

BioBash: Chamber Replicates Success

Austin Winter 2012 BioBash
BioPunks: DIY Scientists Hack the Code of Life
Bob Swanson and Genentech
Epigenetics
Mayim Bialik

OBJECTIFIED

Objectified is a film by Gary Hustwit about design, designers, and the objects that they create.  Dieter Rams of Braun and Apple’s Jonathan Ive appear, of course. (See, The Genius of Design below.)  So do thirty other designers, and a couple of supportive critics, such as Paola Antonelli of the Museum of Modern Art.  IKEA and Target both get cameo roles as they deliver to us the magic of inexpensive mass produced items that ennoble us, their owners, with the spiritual benefits of good design.  You and I also appear in anonymous walk-ons because in the words of Andrew Blauvelt, “anything that is touched by man, is transformed by man, is by its very nature designed.” The human-built environment is design.

Dirt Devil by Karim Rashid

Karim Rashid works for the “techno-organic world.” As a teenager, he owned a Claritone stereo radio and a Braun alarm clock and through his teenage angst, looking at them alone in his room brought a sense of comfort.  He calls our time the “third technological revolution.” To him, our living room furniture is like a kitsch stage prop. “When I get up from my laptop and my iPod, do I get into a horse and carriage? No.”

Claritone stereo similar to Karim Rashid's.

According to Andrew Blauvelt, the design concept has three layers. First form begets form, the formal logic of form.  Then come symbols and symbolism, the cultural symbols.  From that comes the contextual symbolism of making coffee, for instance, the bigger scenario of the human-object relationship.  The little rituals define the fork and knife.  The vacuum cleaners from Dirt Devil and Dyson extended the horizons for a single-use product into designer goods for display. Ultimately, the Roomba programmable robot vacuum allowed an undreamed of level of hacking as user interaction.

Alice Rawsthorn of the International Herald Tribune points out that if you were a Martian and you came to Earth, you could pick up a spoon or a chair and pretty much get a feel for their purpose.  Now, the digital age removes that.  Objects can take any shape.  This leads to tensions and conflicts in design. 

But objects do not take just any shape.  Some seem intractably wedded to their pasts.

Three principals from IDEO of Palo Alto shared a common theme in their different experiences of design.  "I inherited my father’s leather briefcase and it got better with time and I look to passing it on.  I look to designing things for wearing in versus wearing out.  ... I designed the case for the GRiD “Compass” computer in 1987, the first laptop.  When I got it home I realized that the beautiful case and clever latches were irrelevant to the user experience, so I came to study software interfaces.  ...  "

"... because in that moment it moves you,
you have an emotion"
-- Hella Jongerius

Naoto Fukusawa designs hardware interaction. Subconscious actions develop the mind and soul: design dissolving in behavior. “A very important turning point for me was the term "obsessive sketch" by Takahama Kyoshi, the haiku master. When the poet’s sentences are overly visible the audience may become uncomfortable. Japanese ritual is the opposite.” 

Rob Walker of the New York Times Magazine asks rhetoically, when the hurricane is coming and you have twenty minutes to pack, what do you grab? Not the object that got a great review in some design magazine, but the object that means the most to you.

Paola Antonelli insists that “democritization of design is an empty slogan.” According to Paola Antonelli, “design takes revolutions and progress and makes it into objects that we can use.”

Speaking of his work on the MacBook Air and MacBook Pro, Jonathan Ive says that the curse of being a designer is always looking at everything and wondering “why does it have to be that way and not some other way?”

Ad hoc design: wine cork as doorstop

Ad hoc design: section of plastic cup as bicycle fender

I want things that do not exist, that you cannot go out and buy, what is going to happen, not what has happened. – Marc Newson.

Within Karim Rashid's apartment

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Knowledge Maps

Documentation is Specification

The Genius of Design

Art & Copy

Start the Presses

The Genius of Design

“For industrial designers, the world is never enough. They give shape and texture to the world to make it livable—indeed, beautiful—for the rest of us. This fascinating five-part documentary examines the art and science of design and the stuff it shapes, from computer chips to cityscapes and everything in between. See the evolution from artisans’ workshops to industrial mass production, and the profound changes it has wrought in our economy, society, and environment.” – from the promotional.

 Acorn Media 2009

In five episodes running 242 minutes, we meet some of the leading designers who gave us our material world.  They are not engineers. They are not scientists.  The Apple computer was the creation of Wozniak and Jobs, of course, but they did not give it the form we know.  Their Macintosh, their iPod, Sony’s Walkman, all of the furniture in an IKEA warehouse, and even the weapons of war achieved materiality because designers thought long and hard about how real people would use these common objects.

“Meet historians, critics, and legendary contemporary designers, including Dieter Rams (Braun electronics), J Mays (Ford), and Jonathan Ive (Apple), who reveal the thinking behind iconic products such as the VW Beetle, the Eames chair, and the computer desktop. Along the way, discover how design has influenced even the outcome of war.”

At a time when – surprising to us, today - German goods were called cheap AEG launched what may have been the first modern rebranding.  They hired Peter Behrens who created a new AEG typeface for both their advertising and their product labeling. From William Morris and the Arts and Crafts movement to Dieter Rams of Braun, from Henry Ford to Ford Motor’s J Mays, we meet the people and their works and their critics (mostly favorable).  Produced for Athena Learning by Tim Kirby’s team for Wall to Wall Media, the video is supported by the Athena website (here) which delivers biographies of Raymond Loewy, Margarete Schütte-Lihotzk, Henry Charles Eames, Alberto Alessi, and Philippe Starck.  The videos also show us Joe Columbo, Robin Day, Jock Kinneir and Margaret Calvert, Earl Silas Tupper, Verner Panton, Marc Newson, and Michael Graves, among many others.  You may not know the names, but if you ever read a highway sign or sat in a plastic chair, you know their work.  It is not always easy. The graphical user interface was first introduced in 1963.  

Supporting the presentation, the website also delivers a study guide for classrooms, and a booklet with more ideas centered on design failures. 

•  Episode 1:  Ghosts in the Machine: What distinguishes good design from bad design in a consumer product?
• Episode 2: Designs for Living: To what extent is the kitchen in your home “a machine for living”
• Episode 3: Blueprints for War: The British Sten gun was designed as a cheap, easy to manufacture, and ultimately disposable weapon. The German “Tiger” tank was the finest quality motorized cannon possible – and because of that, it could not be produced in sufficient numbers.
• Episode 4: Better Living Through Chemistry: Plastic, for better and worse. Steve Jobs famously said, “You know a design is good when you want to lick it.”
• Episode 5: Objects of Desire: How do you think the challenges of sustainability and limited disposal will affect product design in the decades ahead? Glen Olver Low calls it “Crade to Cradle.”  Instead of being down-cycled, his concept of recycling returns material to the highest level of manufacturing processes.

Michael Graves found his inspiration - in part - at a flea market, where he saw a hand-made stopper, carved as a rooster which sang when the water boiled. The conical shape was dictated by the need to boil water as rapidly as possible.

Previously on Necessary Facts

Objectified: A Film by Gary Hustwit

Art & Copy: How Advertising Changed Our Self-Perceptions

Start the Presses: Typography 

Cities: The Urban Visions of Jane Jacobs
Documentation is Specification

Drones are Everywhere

"The influential head of Google, Eric Schmidt, has called for civilian drone technology to be regulated, warning about privacy and security concerns. Cheap miniature versions of the unmanned aircraft used by militaries could fall into the wrong hands, he told the UK's Guardian newspaper.  Quarrelling neighbours, he suggested, might end up buzzing each other with private surveillance drones.  He also warned of the risk of terrorists using the new technology.  Mr Schmidt is believed to have close relations with US President Barack Obama, whom he advises on matters of science and technology.” -- BBC Technology News here Touted on Slashdot here

Radio controlled model Air Force One Giant Scale RC Airplanes here

Radio Controlled Coast Guard Ship Model

Radio Controlled Crane from ToysRUs

Among the huge, wide, broad and deep array of RC “cars” are replica tanks.  Radio controlled toys mimic just about any mechanism you can imagine. And the technology is 50 years old, back to the first transistors. 

Of course,  good things come in small packages, such as this remote controlled dragonfly.

Back in 1980, the National Association for Rocketry held its annual convention (NARAM 22) in East Lansing. My little sister and I built rockets and went to several launches.  As a result, I heard about the government contracting accomplished model rocket hobbyists to fly cameras over Three Mile Island.  All in all, this is very old technology now.  Altitudes of 2000 meters are typical for record-holders.  The amateur construction record for a rocket is 1648 pounds straight up to 4400 feet, a 1/10 scale Saturn V.

But this should be no surprise.  Wernher von Braun was a member of a club of weekend rocketeers.  When war came, only their social connections gave them access to the decision makers.  They were not sought out by the military or the ruling party.  Even after the effort was funded for militarization, as Willy Ley told it in Rockets, Missiles, and Space Travel, they were thwarted by the need for massive fuel pumps. They began planning a whole enterprise to design and build them.  Then, one of their industrial collaborators told them about fire engines.  The point is that like rockets, military drone aircraft are just an adopted technology. The private sector came first by decades before the military caught on and recognized the new state of the art. 

 Eric Schmidt’s father was Wilson Schmidt, a German American professor of international economics at Johns Hopkins University who worked at the U.S. Treasury Department during the Nixon Administration. … in 2011... Schmidt dated Lisa Shields, a communications executive for the Council on Foreign Relations. ... According to PCWorld, Schmidt also expressed the following sentiment: "if you don’t have anything to hide, you have nothing to fear". ... Schmidt is also a member of the Bilderberg Group. - Wikipedia 

Schmidt is a smart fellow, a Unix wizard who earned his masters wiring up the Berkeley electrical engineering and computer science departments; but, he wants to control your toys. People like him are drawn to centers of political power. That carries a consequence for Google's corporate strategies. Be that as it may, self-propelled, programmed, cybernetic, and autonomic machines have been with us since flyball governors were added to steam engines.

The Science of Liberty

The Science of Liberty: Democracy, Reason, and the Laws of Nature by Timothy Ferris is excellent assembly of cogent essays is an extended argument for freedom and science. The scientific revolution and liberal democracy are inseparable.  To limit one is to defeat the other.  According to Ferris, the scientific method is the root of political freedom.  In that, he continues the case made long ago by Karl Popper in The Open Society and Its Enemies.  

Like Popper, Ferris misses the center of the target.  It is not “liberal democracy” but capitalism that enabled and was empowered by the Enlightenment philosophy of rational-empiricism that we know today as Objectivism. To be fair, though, Ferris does devote an entire chapter to “The Science of Wealth” where he praises both free market capitalism and Adam Smith’s Wealth of Nations.

Anyone who values freedom and science will find this book is well worth the time invested.  The essays are crisp, insightful, and backed by citation.  While Ferris does good work building up the material benefits of the scientific method and the human values in liberal democracy, the core of the book is a total demolition of claims that centralism and totalitarianism can lead to good science.  In one chapter, plus other material throughout, Ferris shows that Nazi Germany and Soviet Russia were scientifically bankrupt, and technologically inferior to the liberal democracies they opposed. 

In just under 300 pages, Ferris delivers a close and informative history of the scientific method, centered on Sir Francis Bacon's creation - and betrayal - of it.  Ancient Greeks such as Aristarchos and Demokritos, guessed correctly, reasoning well, that the Earth orbits the sun, and that matter is comprised of atoms.  But that was not science.  Science is a method of observation, questioning, investigation, tests, and reporting.  (To see why Aristotle's description of the chick embryo does qualify as science, see my review of Great Scientific Experiments, here.)  Science did not exist before the Renaissance; the creation of science led to the political Enlightenment. Like the chicken and the egg, of course, which came first is a moot point: you cannot have one without the other.  More to the point, Ferris argues well, the essence of liberal democracy, what it is that makes freedom work, is precisely the scientific method applied to social problems.

That said, Ferris is well aware of the essential weakness in liberal politics: experimental programs become permanent.  According to the scientific method as applied to civics, we, the people, vote on certain remedies, try them out, and if they fail, we pragmatically try something else.  Actually, that last never happens.  We go on to new attempts, but the old failures continue to be funded and staffed and enforced.  He has no solution for that.

Ferris does deliver a good history, especially of the American revolution as the triumph of citizen scientists.

In another chapter on “Academic Antiscience” Ferris reveals how Karl Popper’s theory of falsification and Thomas Kuhn’s theory of “paradigm” were misapplied at first innocently, and then wantonly, by “post modernists.”  Claiming that theirs was an agenda of liberation, Paul Feyerabend and those who followed him quickly moved on to demanding an end to science and an end to material prosperity.

Supplementing that demonstration is a chapter on Progress.  Post-modernists decry and deny it.  They claim that material progress leaves us spiritually impoverished.  Politically, they claim that progress is illusory, being only the looting of the poor by the rich. Ferris takes the second claim and shreds it with facts.  Even if the claim were true that the rich are evermore far richer than the poorest, the sheer numbers of the poor, multiplied by their material advantages today, bury any claims to injustice from progress.  The poorest are far better off than they were 50 or 100 years ago. 

The book closes with a chapter on global warming and the consequent ice age that will come “unless we do something.”  What is that “we” must “do” is less clear.  Once again, Ferris is mindful of the precarious state of the world’s poor.  Reducing greenhouse gases, however accomplished, must not come by taking their lives. Who can afford to make which sacrifices today in order to secure the future is a tough question for which Ferris has no answer.

“The point is that lightswitch ethics—pounding the table and insisting, “We must save the lives of our grandchildren” or alternately, “We must leave free enterprise alone”—are inadequate. … Responsible stewardship requires dealing in quantities and probabilties, with little recourse to comforting certitudes.” 

Ferris closes by comparing the universal, invariant nature of science with the universal and invariant nature of liberalism.  Both depend on and advocate truths that apply to all people in all times and places.

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Goofing to a Meltdown?

After the Code.Org video touting "fun at work"  (see the post before this one), this article appeared on March 28 on CNN.com about the positive side of "goofing off at work."

The theory is that encouraging "play" at work not only boosts morale but also fosters increased creativity and teamwork, leading to better productivity and quality of work. ...
"The emphasis on fun spawns creative energy," explains Lauren Austin. She's creative director at marketing agency MKG in New York, where play is a priority. "Inspiration comes from interacting with one another and the world around us."

I agree 100% that stepping back from a problem and setting it aside allows the opportunity for creativity and insight.  We all have such experiences and we all know many stories.  Friedrich Kekule solved the problem of benzine's structure while dozing off and staring into a fire.  Kari Mullis had a similar insight about PCR (polymerace chain reactions; how we now replicate DNA), while speeding in his sports car up and through the Sangre de Cristo mountains outside Sante Fe.  But when Pasteur said that chance favors the prepared mind, his emphasis was on the mind, not the chance.

Large social events seldom have a single cause, but certainly do have identifiable contributing factors.  Not everything going on at one moment causes the events of the next.  But human action is causative.  I believe that the Dot.Com Meltdown was caused in part by the "business casual" attitude expressed in acceptable office attire and the casual atmosphere in business of the times.  The prosperity of the 80s and 90s, the Reagan-Clinton years, seemed assured because we never got to the real reason, the root, or radical fact.  Liberty and freedom are requisites to prosperity, but they are not causes of it. 

Cut taxes. Remove regulations.  Wealth will follow.  ... but only if the prepared minds can see for themselves the benefits of their creativity.  The creative mind does not work primarily for money (or primarily for love), but absent those rewards, much less gets done.  Primitive hunters were great artists. They decorated caves and cliffs, their weapons, and themselves.  Naked in the sun, they wore decorative shells for the pleasure of it. ... but the alphabet was waiting... and waiting...

What you can measure you can improve.  The invention of large numbers (beyond 3) led to the creation of writing. And here we are 8,000 years later, living by means that would be inexplicable to our Ice Age ancestors.  The difference is that we learned to work when we did not need to.  We gave up the luxury of hunting in an abundant environment for the opportunity to work long hours every day.  We could measure, count, tally, and store the excess wealth.

Will the new theory of goofing off on the job improve the statements of earnings, or are we on the verge of another Dot.Com Meltdown?

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