Author Archives: luysii

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Consensus isn’t what it used to be.

Technology marches on.  The influence of all 2^20 = 1,048,576 variants of 5 nucleotides on either side of two consensus sequences for transcription factor binding were (1) synthesized (2) had their dissociation constants (Kd’s) measured.  The consensus sequences were for two yeast transcription factors (Pho4 and Cbf1).  [ Proc.  Natl. Acad. Sci. vol. 115 pp. E3692 – E3702 ’18 ] .  The technique is called BET-seq (Binding Energy Topography by sequencing).

What do you think they found?

A ‘large fraction’ of the flanking mutations changed overall binding energies by as much as consensus site mutations.  The numbers aren’t huge (only 2.6 kiloCalories/mole).  However at 298 Kelvin 25 Centigrade 77 Fahrenheit (where RT = .6) every 1.36 kiloCalories/mole is worth a factor of 10 in the equilibrium constant.  So binding can vary by 100 fold even in this range.

The work may explain some ChIP data in which some strips of DNA are occupied despite the lack of a consensus site, with other regions containing consensus sites remaining unoccupied.  The authors make the interesting point that submaximal binding sites might be preferred to maximal ones because they’d be easier for the cell to control (notice the anthropomorphism of endowing the cell with consciousness, or natural selection with consciousness).  It is very easy to slide into teleological thinking in these matters.  Whether or not you like it is a matter of philosophical and/or theological taste.

Pity the poor computational chemist, trying to figure out binding energy to such accuracy with huge molecules like a transcriptional factors and long segments of DNA.

It is also interesting to think what “Molar” means with these monsters.  How much does a mole of hemoglobin weigh?  64 kiloGrams more or less.  It simply can’t be put into 1000 milliliters of water (which weighs 1 kiloGram).  A liter of water contains 1000/18 moles (55.6) moles of water.  So solubilizing 1 molecule of hemoglobin would certainly use more than 55 molecules of water.  Reality must intrude, but we blithely talk about concentration this way.  Does anyone out there know what the maximum achievable concentration of hemoglobin actually is?

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Where are the native Americans ?

When I practiced neurology in Montana in the 70’s and 80’s I would have received some very strange looks from my Crow or Cheyenne patients if I called them ‘native Americans’.  They called themselves Indians and everyone else did too.  Clearly the definition has changed, so it may be OK if I change it again to mean someone who was born in the USA rather than abroad (like my two grandchildren born in Hong Kong).

I sometimes eat breakfast with an electrical engineering prof at the local diner.  I was interested in whether applications to grad school had fallen off.  He said they had.  I assumed that the fall off  was from the middle east, but he said his students were mostly from China and India.  Then he went on and said that Americans (by which I mean native Americans) simply weren’t going for higher degrees in engineering. This was completely different (in Chemistry at least) back in the early 60s.  Our whole cohort was US born and bred, except for one Sikh.  The postDocs were from all over — Scotland, Japan, India (particularly Sikh’s).

 

Well nearly 60 years is a long time, so I asked a family member EE PhD about it.  Here’s what he said

“I don’t have statistics from Berkeley grad school 1975-80, when I was there, but it certainly seemed like U.S.-born grad students were a minority — and a small one — in the EECS department.

One of the issues here is that in many cultures around the world, especially in developing countries, engineers sit at or near the top of the socio-economic heap. So bright students outside the U.S. want to become engineers while bright U.S.-born students want to become medical doctors and lawyers. I’ve heard various comments about this over the years from my foreign colleagues. They find it amusing that medical doctors and lawyers are so venerated here in the U.S.”
It is remarkable that there had been such a change in 15 years.  Granted that the engineers were mostly at MIT, most of the people I knew there in the 60s were American born.
So yesterday at Harvard Graduate Alumni Day, I asked for the (rough) percentage of foreign born grad students (in everything) and was told it was about 1/3.  Also that their applications were up.
This is good for Harvard, but if what is going on at the local State University is typical of the rest of the country it does not bode well for us. Back in the day, a friend said that the universal scientific language was broken English.  Of the 7 Nobels of the Harvard Chemistry department since the 60s, three (Bloch, Hoffmann, Karplus) were born abroad and got out because they were Jewish.  One hid in an attic for 18 months as a child.

An unhappy anniversary

The battle to feed all of humanity is over. In the xxxx’s hundreds of millions of people will starve to death in spite of any crash programs embarked upon now. At this late date nothing can prevent a substantial increase in the world death rate.

Pretty serious stuff.  Written 50 years ago, “The Population Bomb” by Paul Ehrlich had enormous impact.  However the xxxx elision concerned the 1970s.

4 years later The Club of Rome released the following broadside, “The Limits to Growth”Here is a direct quote from the jacket flap.

“Will this be the world that your grandchildren with thank you for? A world where industrial production has sunk to zero. Where population has suffered a catastrophic decline. Where the air, sea and land are polluted beyond redemption. Where civilization is a distant memory. This is the world that the computer forecasts. What is even more alarming, the collapse will not come gradually, but with awsome suddenness, with no way of stopping it”

This sort of stuff is why the elderly (such as myself who will turn 80 this month) gradually become more and more cynical.   Unfortunately, over half the people alive today have no memories of these two debacles.  If you want to read more on this buy a book by a Yale Professor, Paul Sabin called “The Bet” concerning the intellectual conflict between Paul Ehrlich — he of the population bomb and Julian Simon. Ehrlich said we’d run out of just about everything shortly (presumably because of too many people), so economist Simon bet him that we wouldn’t. The intellectual war began in earnest in the 80’s and dragged on for a decade or so. I recommend the book and I think it really does capture the flavor of the times and the debate.  In it you will find John Holdren, Obama’s science advisor, also a devout malthusian, although with a degree in physics.

The current barrage over global warming seems to be diminishing.  Particularly damning is the failure of the models to predict the absence of any change in global temperature for 17 years.  I tried not to be turned off by the similarly apocalyptic and Old Testament Prophetic tone of the proponents.  But any scientific theory to  be any good (aside from Evolution, and String theory) must make testable predictions, and those about climate have consistently failed for 20 years.

A research idea yours for the taking

Why would the gene for a protein contain a part which could form amyloid (the major component of the senile plaque of Alzheimer’s disease) and another part to prevent its formation. Therein lies a research idea, requiring no grant money, and free for you to pursue since I’ll be 80 this month and have no academic affiliation.

Bri2 (aka Integral TransMembrane protein 2B — ITM2B) is such a protein.  It is described in [ Proc. Natl. Acad. Sci. vol. 115 pp. E2752 – E2761 ’18 ] http://www.pnas.org/content/pnas/115/12/E2752.full.pdf.

As a former neurologist I was interested in the paper because two different mutations in the stop codon for Bri2 cause 2 familial forms of Alzheimer’s disease  Familial British Dementia (FBD) and Familial Danish Dementia (FDD).   So the mutated protein is longer at the carboxy terminal end.  And it is the extra amino acids which form the amyloid.

Lots of our proteins form amyloid when mutated, mutations in transthyretin cause familial amyloidotic polyneuropathy.  Amylin (Islet Amyloid Polypeptide — IAPP) is one of the most proficient amyloid formers.  Yet amylin is a protein found in the beta cell of the pancreas which releases insulin (actually in the same secretory granule containing insulin).

This is where Bri2 is thought to come in. It is also found in the pancreas.   Bri2 contains a 100 amino acid motif called BRICHOS  in its 266 amino acids which acts as a chaperone to prevent IAPP from forming amyloid (as it does in the pancreas of 90% of type II diabetics).

Even more interesting is the fact that the BRICHOS domain is found in 300 human genes, grouped into 12 distinct protein families.

Do these proteins also have segments which can form amyloid?  Are they like the amyloid in Bri2, in segments of the gene which can only be expressed if a stop codon is read through.  Nothing in the cell is perfect and how often readthrough occurs at stop codons isn’t known completely, but work is being done — Nucleic Acids Res. 2014 Aug 18; 42(14): 8928–8938.

I find it remarkable that the cause and the cure of a disease is found in the same protein.

Here’s the research proposal for you.  Look at the other 300 human genes containing the BRICHOS motif (itself just a beta sheet with alpha helices on either side) and see how many have sequences which can form amyloid.  There should be programs which predict the likelihood of an amino acid sequence forming amyloid.

It’s very hard to avoid teleology when thinking about cellular biochemistry and physiology.  It’s back to Aristotle where everything has a purpose and a design.  Clearly BRICHOS is being used for something or evolution/nature/natural selection/the creator would have long ago gotten rid of it.  Things that aren’t used tend to disappear in evolutionary time — witness the blind fish living in caves in Mexico that have essentially lost their eyes. The BRICHOS domain clearly hasn’t disappeared being present in over 1% of our proteins.

Suppose that many of the BRICHOS containing proteins have potential amyloid segments.  That would imply (to me at least) that the amyloid isn’t just junk that causes disease, but something with a cellular function. Finding out just what the function is would occupy several research groups for a long time.   This is also where you come in.  It may not pan out, but pathbreaking research is always a gamble when it isn’t stamp collecting.

 

Homology: the skinny

I’d love to get a picture of a triangulated torus in here but I’ve tried for hours and can’t do it.

Homology is a rather esoteric branch of topology concerning holes in shapes (which can have any number of dimensions, not just two or three.  It is very easy to get bogged down in the large number of definitions and algebra without understanding what is really going on.  I certainly did.

 

The following explains what is really going on underneath the massive amounts of algebra (chains, cycles, chain groups, Betti numbers, cohomology, homology groups etc. etc.) required to understand homology.

The doughnut (torus) you see just above is hollow like an inner tube not solid like a donut.  So it is basically a 2 dimensional surface in 3 dimensional space.  Topology ignores what its objects of study (topological spaces) are embedded in, although they all can be embedded in ‘larger’ spaces, just as the 2 dimensional torus can be embedded in good old 3 dimensional space.

 

Homology allows you to look for holes in topological spaces in any dimension.  How would you find the hole in the torus without looking at it as it sits in 3 dimensioal space.

 

Look at the figure.  Its full of intersecting lines.  It is an amazingly difficult to prove theorem that every 2 dimensional surface can be triangulated (e.g. points placed on it so that it is covered with little triangles).  There do exist topological objects which cannot be triangulated (but two dimensional closed surfaces like the torus are not among them).

 

The corners of the triangles are called vertexes.  It’s easy to see how you could start at one vertex, march around using the edges between them and then get back to where you started.  Such a path is called a cycle.  Note that a cycle is one dimensional not two.

 

Every 3 adjacent vertices form a triangle. Paths using the 3 edges between them form a cycle.  This cycle is a boundary (in the mathematical sense) because it separates the torus into two parts.  The cycle is one dimensional because all you need is one number to describe any point on it.

 

So far incredibly trivial?  That’s about all there is to it.

 

No go up to the picture and imagine the red and pink circles as cycles using as many adjacent vertices as needed (the vertices are a bit hard to see). Circle
Neither one is a boundary in the mathematical sense, because they don’t separate the torus into two parts.

 

 

Each one has found a ‘hole’ in the torus, without ever looking at it in 3 dimensions.

 

 

So this particular homology group is the set of cycles in the torus which don’t separate it into two parts.

 

 

Similar reasoning allows you to construct paths made of 3 dimensional objects (say tetrahedrons instead of two dimensional triangles) in a 4 dimensional space of  your choice.  Some of these are cycles separating the 4 dimensional space into separate parts and others are cycles which don’t.  This allows you to look for 3 dimensional holes in 4 dimensional spaces.

 

 

Of course it’s more complicated than this. Homology allows you to look for any of the 1, 2, . . , n-1 dimension holes possible in an n dimensional space — but the idea is the same.

 

There’s tons more lingo to get under your belt, boundary homomorphism, K complex, singular homology, p-simplex, simplicial complex, quotient group, etc. etc. but keep this idea in mind.

 

Amyloid again, again . . .

Big pharma has spent (and lost) several fortunes trying to attack the amyloid deposits of Alzheimer’s.  But like my late med school classmate’s book — “Why God Won’t Go Away” ==https://www.amazon.com/Why-God-Wont-Go-Away/dp/034544034X, amyloid won’t go away either.   It’s a bit oblique but some 300 of our proteins contain a 100 amino acid stretch called BRICHOS.  Why? Because it acts as a chaperone protein preventing proteins with a tendency to form amyloid from aggregating into fibrils.   The amino acids form a beta sheet surrounded front and back by a single alpha helix.

[ Proc. Natl. Acad. Sci. vol. 115 pp. E2752 – E2761 ’18 ] Discusses Bri2 (aka Integral Transmembrane protein 2B (ITM2B), a 266 amino acid type II transmembrane protein. Bri2 contains a carboxy terminal domain Bri23 released by proteolytic processing between amino acids #243 #244 by furinlike proteases. Different missense mutations at the stop codon of Bri2 cause extended carboxy terminal peptides called  Abri or Adan to be released by the proteases. Abri produces Familial British Dementia (FBD) and Adan produces Familial Danish Dementia (FDD). Both are associated with amyloid deposition in blood vessels, and amyloid plaques throughout the brain along with neurofibrillary tangles.

What is fascinating (to me) is that the cause and cure are both present in the same molecule Bri2 also contains a BRICHOS domain.  This implies (to me) that possibly the segment possibly forming amyloid is being used by the cell in some other fashion.

Bri2 is found in the beta cell of the pancreas (produces insulin).  The beta cell also produces Islet Amyloid PolyPeptide (IAPP  aka amylin ) one of the most potent amyloid forming proteins known.  Nonetheless the pancreas makes tons of it, and like insulin, is secreted by the beta cell in response to elevated blood glucose.  The present work shows that Bri2 is what keeps IAPP from forming amyloid.  The BRICHOS segment (amino acids #130 – #231) is released from Bri2 by ADAM10 (you don’t want to know what the acronym stands for).

How many of the 300 or so human proteins containing the BRICHOS domain also have amyloid forming segments.  If they do, this implies that the amyloid forming segments are doing something physiologically useful.

 

 

Res ipsa loquitur

I received the following Email from harvard_magazine@harvard.edu today.  It is such a parody of political correctness gone mad that it might be fake news.  If so I’ll retract it.

Here it is unedited.

THE COLLEGE’S policy to sanction members of unrecognized single-gender social organizations (USGSOs) won’t require that students make an oath-like affirmation that they don’t belong to such clubs. That controversial measure had originally been recommended in a March 2017 report to College dean Rakesh Khurana by a committee examining implementation. Dean of students Katie O’Dair, whose office is tasked with enforcing the policy, announced the implementation plan in an email to College students this morning; the Office of Student Life (OSL) has created a website with details.

The policy, as previously reported, prohibits students who have belonged to single-gender social organizations (including final clubs and Greek organizations) within the previous year from receiving College endorsement for fellowships, or holding leadership positions in recognized student organizations or athletic teams. It applies to students matriculating in the fall of 2017 (current freshmen) or later. The Harvard Corporation voted to retain the sanctions in December, after a year and a half of intense debate across the Harvard community that included concerns over gender equality, students’ freedom of association, and faculty governance of the College.

OSL appears to have created a less punitive plan than what was recommended by last year’s implementation committee, in response, presumably, to widespread criticism of the recommendation that students make an oath-like affirmation of their compliance with the policy. “We are approaching this with trust, honesty, and transparency,” O’Dair said in an interview. “What we did not accept is any pledge or affirmation by students.”

“We are not going to take any efforts to go find students” in violation of the policy, she added. Instead, it will be enforced similarly to other misconduct issues (such as the alcohol policy), which generally prompt a disciplinary process only when violations have escalated enough to be brought to the administration. The College also won’t accept anonymous reports of policy violations.

The policy will be added to the Handbook for Students, which means that it will have to come before the faculty for discussion and debate (prior ambiguity about whether the faculty could debate the language was a point of contention last year).

The sanctions will affect all fellowships administered by the Office of Undergraduate Research and Fellowships: not just top fellowships like the Rhodes and Marshall scholarships, but also Harvard-specific programs like the Harvard-Cambridge Scholarship. Student groups affected will include official student organizations, pre-orientation programs, Phillips Brooks House Association programs, and athletic teams. The policy won’t affect members of The Harvard Crimson or the Undergraduate Council (the implementation committee had recommended these organizations be included, which Khurana did not accept because of their independent nature).

OSL is working with some single-gender social groups, including male and female final clubs, to become gender-inclusive. Such groups are “on the path to compliance,” associate dean of student engagement Alexander Miller said, and membership in those entities will not be sanctioned. Throughout the spring and summer, OSL will develop criteria for such groups to be considered compliant with College regulations for recognized student organizations. (Last year’s implementation committee recommended, for example, that they be required to publicly list their demographic makeup). It’s still unclear what will be required, and depending on what the final plan looks like, members of a group that becomes co-ed but doesn’t want to become recognized by the College in any official capacity (for example, to avoid regulation) may still be subject to sanctions.

“We feel very positive about the impact of this policy on campus,” O’Dair said. “Certainly there will be groups that want to continue, as is their choice, to be single-gender-focused, and all we would ask is they inform their prospective members in their recruitment of the policy.”

OSL will also create a framework for governing social groups, envisioned as a new category of recognized student organizations. “When you bring to campus social organizations that are fully around the idea of socializing, there are things that I would have to think about from where I sit that I wouldn’t have to think about with the math club,” Miller explained. “There’s a lot of liability when you throw a bunch of College students in a room to socialize.”

Violations “will be reviewed via the College’s usual processes for addressing concerns about community standards,” the policy states. “As described in the Handbook, issues relating to social misconduct are reviewed by the Administrative Board, while concerns related to academic integrity and the Honor Code are reviewed by the Honor Council.” The expectation is that violations will be heard by the Ad Board (and not the Honor Council, which was created expressly to investigate violations of academic conduct); the dean of the College will determine the appropriate adjudicating organization if questions about jurisdiction arise.

Although the implementation committee recommended a five-year “bridge period” to give women’s organizations extra time to transition to gender-inclusive membership, OSL has not adopted that recommendation. Instead, OSL will provide “dedicated support” to women’s organizations that want to transition to gender-inclusive membership. “[W]e welcome all organizations, and especially those whose membership is currently restricted to women, to partner with us,” the policy states. “Heidi Wickersham, Program Manager at the Harvard College Women’s Center, and staff members in the Office of Student Life will jointly partner with groups wishing to transition from having a women’s exclusive membership while maintaining a women’s-focused mission.”  ”

The same issue (May June) has an article title “The Mirage of Knowledge” with subtitle “Tom Nichols dissects the dangerous antipathy to expertise”.  They actually wonder why. Harvard has harnessed its expertise to find the single perfect, true and good form of social organization and be damned if you don’t like it.

In a way Harvard is returning to their Puritan antecedents.  Look what they did to Roger Williams. Here’s a bit from the Wikipedia entry –https://en.wikipedia.org/wiki/Roger_Williams — “Williams was expelled by the Puritan leaders from the Massachusetts Bay Colony for spreading “new and dangerous ideas”, and he began settling the Providence Plantations as a refuge offering what he called “liberty of conscience” in 1636. In 1638, he founded the First Baptist Church in America, also known as the First Baptist Church of Providence.”

The old social tropes keep coming back.  What else but the Salem witch trials could the treatment of the Amirault’s be? — https://en.wikipedia.org/wiki/Gerald_Amirault

Stephen Hawking R. I. P.

Stephen Hawking, brilliant mathematician and physicist has died.  Forget all that. He did something for my patients with motor neuron disease that I, as a neurologist, could not do.  He gave them hope.

What has chemistry done for them?  Quite a bit, but there’s so much left.

Chemistry, when successful, just becomes part of the wallpaper and ignored. All genome sequencing depends on what some chemist did.

For one spectacular example of what, without chemistry, would be impossible is Infantile Spinal Muscular Atrophy (Werdnig Hoffmann disease).  For the actual molecular biology behind it — please see — https://luysii.wordpress.com/2016/12/25/tidings-of-great-joy/.   Knowing the cause has led to not one but two specific therapies — an antisense oligonucleotide and a virus which infects neurons and actually changes the gene.

So knowing what the cause of a disease is should lead to a treatment, shouldn’t it?  Hold that thought.  Sometimes one form of motor neuron disease (amyotrophic lateral sclerosis or ALS) can be hereditary.  Find out what is being inherited to find how ALS is caused.

Well, the first protein in which a mutation is associated with familial ALS (FALS) was found exactly 25 years ago.  It is called superoxide dismutase (SOD1).  Over 150 mutations have been found in the protein associated with FALS, and yet despite literally thousands of papers on the subject we don’t know if the mutations cause a loss of function, a gain of function (and if so what that function is), an increased tendency to fold incorrectly, and on and on and on.  It’s a fascinating puzzle for the protein chemist and over the years my notes on the papers I’ve read about SOD1 have ballooned to some 25,000 words.

If you’re tired of working on SOD1, try a few of the other proteins in which mutations have been associated with FALS — Alsin, TAF15, Ubiquilin, Optineurin, TBK1 etc. etc.  The list is long.

Now it’s biology’s turn.  Motor neurons go from the spinal cord (mostly) and brain to produce muscle contraction.  Why should only this tiny (but crucial) minority of cells be affected.  The nerve fibers leave the spinal cord and travel to muscle in nerves which contain sensory nerve fibers making the same long trip, yet somehow these nerves are spared.

More than that, why should these mutations affect only these neurons, and that often after decades.  Also why should great athletes (Lou Gehrig, Ezzard Charles, etc. etc. ) get the disease.

One closing point.  Hawking shows why, in any disease median survival (when 50% of those afflicted die) is much a more meaningful statistic than average duration of survival.  Although he gave my patients great hope, they all died within a few years even as he mightily extended average survival.

 

Hillary Clinton’s latest health event

On a recent trip to India Hillary clearly had difficulty placing her left foot and nearly fell down a set of stairs twice.  You can watch the video on the following website http://dailycaller.com/2018/03/12/hillary-falls-down-stairs-india/.  Please ignore all the snarkiness of the commentary and just look at the video over and over.  She comes out of an old building and starts going down some worn stone steps linking her left arm into that of a large man.  Stop the video when she begins to fall and notice how she placed her left foot.  Fortunately you can go back and forth as many times as you wish.  It clearly wasn’t where it should have been. The same thing happened with her second near fall.  Then watch the way she places her left leg as she walks to the car.  It’s as though she doesn’t really know where it is.

This all fits with my opinion that she suffered a stroke in December of 2012.  The press bought what I thought was a rather hokey explanation that it was traumatic in origin.  At any rate we do know that she had a blood clot in a vein and had double vision lasting for several weeks.  You can read the reasoning behind this here — https://luysii.wordpress.com/2012/12/31/medical-tribulations-of-politicians-degrees-of-transparency/

Then during the campaign in 2016 at an event to commemorate 9/11 she fainted.  The press cast this as a stumble, but I don’t think it was. Once again you have a video of the event with a link to it in a post about the event — https://luysii.wordpress.com/2016/09/13/hillarys-fainting-spell/.  As Richard Pryor famously said when his wife caught him with another woman. He denies anything is going on, and asks his wife, “Who you gonna believe, me or your lying eyes?”

So what does this retired neurologist and former board examiner think is going on?  Given the little released about her health there are many possibilities.  Statistically people who have had one stroke have around a 6% chance of another one in a given year (each and every year).  Given the way she didn’t seem to know where her left foot was, a stroke in the right parietal region is a possibility.

It is clear that the original area of neurologic deficit in 2012 – 13 was in the brainstem, as it affect the nerves to her eyes.  This is an area intimately involved in coordination, but (fortunately) not in thinking.  So she may have suffered a further stroke in this area.  We don’t know if she’s still taking a blood thinner.

She did look pretty frail, and it’s fortunate for her health that she doesn’t have the stresses of the presidency to deal with.

Addendum 14 March: Apparently she tripped/fell/passed out while on a tour in England breaking a toe 6 months ago http://www.foxnews.com/politics/2017/10/16/hillary-clinton-book-tour-stumbles-after-ex-candidate-falls-and-hurts-foot.html

You don’t have to go to medical school or take a neurology residency to know that a 70 year old woman with 4 neurological events in the past 5 years and 3 months is not in good shape.

Addendum 15 March: Unfortunately she’s had another fall, resulting in a fractured wrist since the episode on the stairs. Here’s the report — https://timesofindia.indiatimes.com/india/hillary-clinton-injured-during-rajasthan-visit/articleshow/63290246.cms

It all adds up to a significant neurological problem with balance.

Who will Jerry Gardner be rooting for ?

The University of Pennsylvania just beat Harvard to become Ivy league champions.  Their reward?  They get to play the top seed (Kansas) in March Madness. A medical school classmate  at Penn (Jerry Gardner) was an all American from Kansas in 1962. He played semipro ball to help pay his way through med school. It was awe inspiring to be in a pickup BBall game with him.

I wonder who he’s going to root for come March 15th.

Jerry had a brilliant career. Here are a few things he did — Former Chief Digestive Diseases Branch, NIH. Held 1st IND for Omeprazole. Conducted clinical studies with PPIs and H2RAs. Analyzed gastric and esophageal pH recordings ….

Here’s a link to what Jerry is doing now — http://www.scifororg.com/about.html.

In addition to being very smart Jerry’s  a very nice guy.

One story from our 50th medical school reunion.  Jerry was still quite trim, but using a cane as he’d just had a hip replacement.  He noted that the rules had changed, and that he still had a year of eligibility left if his hip continued to improve.