Raghuveer Parthasarathy: Four Physical Principles and Biophysics -- Manifold podcast #11

 

Raghu Parthasarathy is the Alec and Kay Keith Professor of Physics at the University of Oregon. His research focuses on biophysics, exploring systems in which the complex interactions between individual components, such as biomolecules or cells, can give rise to simple and robust physical patterns. 

Raghu is the author of a recent popular science book, So Simple a Beginning: How Four Physical Principles Shape Our Living World. 

Steve and Raghu discuss: 

0:00 Introduction 

1:34 Early life, transition from Physics to Biophysics 

20:15 So Simple a Beginning: discussion of the Four Physical Principles in the title, which govern biological systems 

26:06 DNA prediction 

37:46 Machine learning / causality in science 

46:23 Scaling (the fourth physical principle) 

54:12 Who the book is for and what high schoolers are learning in their bio and physics classes 

1:05:41 Science funding, grants, running a research lab 

1:09:12 Scientific careers and radical sub-optimality of the existing system 

Transcript.

Resources: 

Book - https://press.princeton.edu/books/hardcover/9780691200408/so-simple-a-beginning 

Raghuveer Parthasarathy's lab at the University of Oregon - https://pages.uoregon.edu/raghu/ 

 

Raghuveer Parthasarathy's blog the Eighteenth Elephant - https://eighteenthelephant.com/

Added from comments:

key holez • 2 days ago 

It was a fascinating episode, and I immediately went out and ordered the book! One question that came to mind: given how much of the human genome is dedicated to complex regulatory mechanisms and not proteins as such, it seems unintuitive to me that so much of heritability seems to be additive. I would have thought that in a system with lots of complicated,messy on/off switches, small genetic differences would often lead to large phenotype differences -- but if what I've heard about polygenic prediction is right, then, empirically, assuming everything is linear seems to work just fine (outside of rare variants, maybe). Is there a clear explanation for how complex feedback patterns give rise to linearity in the end? Is it just another manifestation of the central limit theorem...?

steve hsu 

This is an active area of research. It is somewhat surprising even to me how well linearity / additivity holds in human genetics. Searches for non-linear effects on complex traits have been largely unsuccessful -- i.e., in the sense that most of the variance seems to be controlled by additive effects. By now this has been investigated for large numbers of traits including major diseases, quantitive traits such as blood biomarkers, height, cognitive ability, etc. 

One possible explanation is that because humans are so similar to each other, and have passed through tight evolutionary bottlenecks, *individual differences* between humans are mainly due to small additive effects, located both in regulatory and coding regions. 

To genetically edit a human into a frog presumably requires many changes in loci with big nonlinear effects. However, it may be the case that almost all such genetic variants are *fixed* in the human population: what makes two individuals different from each other is mainly small additive effects. 

Zooming out slightly, the implications for human genetic engineering are very positive. Vast pools of additive variance means that multiplex gene editing will not be impossibly hard...

This topic is discussed further in the review article: https://arxiv.org/abs/2101.05870

Rigorous inequalities

The Effects of an Anti-grade-Inflation Policy at Wellesley College
Journal of Economic Perspectives, 28(3): 189-204 (2014)
DOI: 10.1257/jep.28.3.189

Average grades in colleges and universities have risen markedly since the 1960s. Critics express concern that grade inflation erodes incentives for students to learn; gives students, employers, and graduate schools poor information on absolute and relative abilities; and reflects the quid pro quo of grades for better student evaluations of professors. This paper evaluates an anti-grade-inflation policy that capped most course averages at a B+. The cap was biding for high-grading departments (in the humanities and social sciences) and was not binding for low-grading departments (in economics and sciences), facilitating a difference-in-differences analysis. Professors complied with the policy by reducing compression at the top of the grade distribution. It had little effect on receipt of top honors, but affected receipt of magna cum laude. In departments affected by the cap, the policy expanded racial gaps in grades, reduced enrollments and majors, and lowered student ratings of professors.

Jim Schombert and I discovered similar disparities in our study of University of Oregon student grades. The inequities would be even larger after controlling for student ability. Eventually employers may demand learning outcomes testing (see Measuring college learning outcomes: psychometry 101), and the results won't be pretty.

Via Carl Shulman and orgtheory.

GameDay: Spartans vs Ducks

The Spartans hung in there (amazing that they were leading at the half) but ultimately the Ducks were too much.

I started out in the Spartan section but I went up to the Oregon President's box at halftime.

My t-shirt says "Spartan For Life" -- didn't go over very well with the Oregon fans! I took abuse everywhere except in the elitist box.

This is very Eugene: a human traffic jam crossing the footbridge over the Willamette river.

Back in Eugene

New UO science building:

Setting up for ESPN College GameDay:

Across the river to the stadium:

Ducks and Spartans play tomorrow:

I'm wrestling with divided loyalties. I've been a big Marcus Mariota fan since he came to UO, and I'd like to see him win a Heisman and a national title.


Craft brewing mecca:

Last days in Oregon

The junk on my whiteboard when I cleaned out my UO office.

Physics building (home of perhaps the largest Feynman diagram in the world):

Buy my house:

NRC physics ranking by research output

I was pleasantly surprised by the recent NRC rankings of physics departments. In the research output ranking, UO did quite well. NRC uses a sophisticated statistical method that gives a range of possible outcomes.

In the list below I would say MIT and Stanford deserve higher ratings, and UO is (alas) ranked higher than it deserves. Once you get beyond the top 10 or so physics departments, there are many good programs across the country, and it's hard to differentiate between them.

Human capital, globalization and physics 101

In the past few years we have seen a large influx of undergraduate students from China. Since UO non-resident tuition is about $20k per annum, these students must come from relatively affluent families there. The conventional wisdom among professors familiar with China is that most of these kids are slackers -- they didn't do well enough on the gaokao to be admitted to a top Chinese university. How good are "slackers" from China? Judge for yourself.

Below is the score distribution from the course I taught this fall, physics 101 for non-majors (about 200 students total). The black histogram is non-Chinese, the red is Chinese, most of whom, judging by their names, are from PRC. Why was this analysis necessary? Because I noticed the score distribution was very different from previous times I had taught the course. About 20-30 PRC kids scored higher than what is usually the highest score. (Click for larger version.)



Here are two exam problems.

An ant slowly pushes a box of mass .1 kg and coefficient of friction .1 a distance of 10m, moving at constant speed. Calculate the work done.

A satellite orbits the Earth at a distance of 3 Earth radii from the center. Compute its gravitational acceleration.

Solvay 1927

1927 Solvay meeting on quantum mechanics. Leading physicists to world: Go Oregon Ducks!




Our grad students modified the famous photo (using Gimp) for the UO Physics t-shirt :-)





Video from the meeting:

Superhumans

Eugene ("Track Town USA") has a long history in running (for instance, Nike was founded here) and hosts a number of high profile track meets during the spring and summer. One of the things I enjoy about these meets is that while they are here I often bump into superhumans (world class athletes) around town, like at the cafe or ice cream shop :-)

Speaking of superhumans, below is a picture of decathlete Ashton Eaton, who may soon have a claim on the title World's Greatest Athlete. The last time (2009) the USATF National Championships were here in Eugene, I predicted great things ahead for him. Eaton, then only a junior, placed second in the US championships. This year (competition completed yesterday) he won by a huge margin, with a total that is the 5th best all-time US score and 13th best in the world. Eaton has incredible times in the sprints (PRs around 10.3, 13.3, 46, IIRC) and is still just learning the technical aspects of the high jump and the throws. In the next few years he could break the world record.



Two winters ago UO had a family day at the rec center, and invited some prominent athletes to spend time with the kids. My twins got to play dodgeball with Eaton for about half an hour -- there were no other families on the court. Eaton took it easy on them :-) When they get older I'll remind them about their time with the World's Greatest Athlete!

Summer in Eugene

One week until the USATF National Championships come to Eugene.




View from the deck :-)




New Ed. school building.



We have fancy organic slow food carts on campus.








This was actually taken back in Taipei, but it fits the summer theme. Why are my kids so much better looking than I am? :-)

Swoosh!

How the athletic shoe was born in Eugene, Oregon. Bill Bowerman was Phil Knight's track coach at U Oregon. Together, they founded Nike.

William Jay "Bill" Bowerman (February 19, 1911 – December 24, 1999) was an American track and field coach and co-founder of Nike, Inc. Over his career, he trained 31 Olympic athletes, 51 All-Americans, 12 American record-holders, 24 NCAA champions and 16 sub-4 minute milers. During his 24 years as coach at the University of Oregon, the Ducks track and field team had a winning season every season but one, attained 4 NCAA titles, and finished in the top 10 in the nation 16 times.

Oregonian: ... Phil Knight is Nike's well-known business and marketing brain, but Bowerman was its mad scientist. His eureka moment came one Sunday morning in 1971 in that house overlooking the McKenzie River.

Bill and Barbara were fixing breakfast -- Barbara wasn't at church, a common mis-telling -- as Bill raised a familiar topic: how to make shoes lighter and faster. Oregon's Hayward Field was transitioning from a cinder to an artificial-surface track, and Bill wanted a sole without spikes that could grip equally well on grass or bark dust.

"It was one of the few (footwear-related) things he ever talked to me about, so it was kind of fun for me," Barbara told Reames in an interview he conducted for Nike in 2006. "I picked out a couple pieces of jewelry and things that had stars on them, or things that we thought would indent or make a pattern on the soles. We were making the waffles that morning and talking about (the track).

"As one of the waffles came out, he said, 'You know, by turning it upside down -- where the waffle part would come in contact with the track -- I think that might work.'

"So he got up from the table and went tearing into his lab and got two cans of whatever it is you pour together to make the urethane, and poured them into the waffle iron."

Bill's breakthrough spawned Nike's Waffle Trainer, released in 1974, the first innovation in a company that became known for them. Before it, most athletic soles were flat with shallow patterns. The waffle had nubs that protruded like the tread on a motorcycle tire.

The distinctive shoe took off, Nike's "air" technology used in Air Jordan basketball shoes soon followed, and the Swoosh was on its way to becoming the top-selling athletic brand in the world.

Future champions at Hayward Field:

Eugene, Oregon

It's strange but very pleasant to be back after 5 months :-) Unfortunately only for a few days.


Sunrise in Eugene.



Physics building.






Institute for Theoretical Science.



Physicists in action! (DOE review presentation.)

Go Ducks

The U Oregon Ducks are ranked #1 in college football, after a decisive win over USC yesterday (highlights). Even the NYTimes has taken notice :-)

NYTimes: ... To combat the notion that U.S.C. is down in talent, Kelly pointed out that on the Trojans’ 44-man depth chart they had 12 five-star recruits and 26 four-star recruits. Kelly then countered that Oregon has zero five-star recruits and 11 four-star recruits.

“They’re still living in the glory days from when Bush was here,” Oregon cornerback Cliff Harris said after the game, referring to Reggie Bush. “They get all these recruits. They thought their talent and five-star recruits was going to beat our hard work. Talent doesn’t beat hard work.”

[See related post: Success vs Ability. I used to love the Nebraska teams of the 80s and early 90s -- few blue chip recruits, but an amazing work ethic that transformed walk ons into top players.]

... What Kelly hints at, but never directly says, is that Oregon’s system has put it ahead of everyone else right now. The Ducks practice only two hours a day without running wind sprints, relying on a tempo so frenetic that it has enabled the Ducks to get into better condition than everyone else. The result? To slow down Oregon’s tempo and get substitutions in the game, teams like Arizona State and Stanford resorted to faking injuries.

One impressed bystander to Oregon’s blurring rise to the top of college football has been Tony Dungy, the former N.F.L. coach whose son Eric is a reserve freshman receiver for the Ducks.

“It’s more mental conditioning,” said Tony Dungy, now an analyst for NBC. “It puts such a strain on you, like Georgetown back when John Thompson was there and they were pressuring and attacking you. At some point, you say, ‘I need a break for a couple of minutes.’ Mentally, teams fatigue more than physically.”

In the back row of Kelly’s news conference under a makeshift tent at the Coliseum, an impressed observer sat stoically, wearing a black Oregon hat and a stylish sport coat. The man, Phil Knight, a Nike co-founder who knows a thing or two about innovation and leaving the competition behind, beamed as Kelly deflected query after query. Knight is Oregon’s chief booster and benefactor, who smiled broadly as he recalled the public address announcer at Oregon’s Autzen Stadium saying he had waited 43 years to introduce the Ducks as the country’s No. 1-ranked team.

US Track and Field Championships in Eugene

The USATF championships were held here again last week and over the weekend. I run on the same track as these guys, only much slower :-)

The photo below is of Eugenian Nick Symmonds (Oregon Track Club Elite) winning the 800m. See also this panorama shot, which shows the 800m finish and all of Hayward Field.



If you're a track fan, keep your eye on Ashton Eaton, who placed second in the decathalon despite being only a junior at UO (he won the NCAAs earlier in the spring).



Complete results from USATF web site.