FATEFUL TIME

 It would be hard to overestimate the fateful aspect of two battles that are now reaching frenzied pitch. The domestic ultra Right tastes blood in the snafu that threatens “Obamacare”; they are gleefully throwing everything into their last, best chance to overturn any expansion of health care. A “broader” coalition, both domestic and international, is feverishly doing its all to abort efforts at easing tensions with Iran.

To see how much is at stake is not to exaggerate the advances contained in the Affordable Care Act, nor is it to overlook imperial self-interests that favor realignment in the Middle East.

What stands out starkly on both issues is the directness of the collision with extreme elements that hope to reverse their political fortunes and dominate America’s course after the Obama years. Internationally, Netanyahu’s regime and Saudi Arabia hope to lock the US into permanent military commitment to their exclusive favored status, including to Israel’s occupation and further expansion and, most notably, to war on Iran.

Given the hysterical assault from the GOP and Netanyahu, it is no small thing that Obama has decided to hold firm so far on both crucial issues. That’s all the more important because the Administration has often disappointed (“surveillance” and drone policies, by way of example). It is also noteworthy that the negotiations with Iran override the stance of many Democrats in Congress who are no less than Republicans in thrall to Netanyahu.

These are very big battles. Right now, a majority of Americans are highly skeptical of “Obamacare”. And most of Congress buys into racist myths of Israeli superiority over Palestinians (and Arabs in general). On the other hand, the vast majority rejects the Tea party and the nihilist obstructionism of the GOP. And almost all of humanity, Americans certainly included, won’t abide the deliberate risk of more war. That was unmistakable in the recent historic uproar that prevented a US military strike in Syria.

There are other issues no less important over time. Some, such as immigrant rights, will have a potent political impact in the months ahead. Here I'm putting in focus the two battles in which the Right sees the chance to take the offensive, to defeat hallmark programs and initiatives that bear the Obama stamp — and so to shift political momentum and take control. 

* * * * * *

A comment on Israel and the nuclear weapons issue: 

It is generally conceded that a military strike against Iran would not eliminate the knowledge, will or capacity for attaining nuclear “equality”.

How far into a future of war is Israel, or the United States, prepared to go? If the Middle East is engulfed in war, can the eventual spread of nuclear rivalry be averted? Can Israel maintain a nuclear monopoly when the United States itself failed at that? And when it comes to a time of desperation, can anyone be sure who would be the first to resort to the bomb? Can we be sure that Rightist extremists of one country would act more responsibly toward humanity than those of another?

Wouldn’t Israel and the world be safer, if universal action toward nuclear disarmament became the cornerstone of nuclear non-proliferation? Converting the Middle East into a zone free of nuclear weapons might well be the key “bargaining chip” for general peace.

PAST 90: IMMUNOLOGY — A Return Journey

 

Past 90 (8)

Now long after retirement, I have all but lost connection with my years of research and teaching in immunology, the molecular and cell biology of the immune system. Once in a while I feel pangs of nostalgia and regret that I have allowed so significant a separation from my long and memorable active years on the UC Berkeley faculty.

That’s the background for my impulse to “catch up” when I heard about a new book: The Compatibility Gene: How Our Bodies Fight Disease, Attract Others, And Define Ourselves, Daniel M. Davis (Oxford University Press). My comments here are not directed at suggesting that most of my op-ed friends should read the book. It’s never easy to make a complex area of science accessible even to interested “outsiders”. But for me, the book served as an intellectual and emotional reawakening to the remarkable advances in our understanding of the immune system.

By the time I got involved in immunology, beginning as a chemistry graduate student in1958, what Davis calls a “scientific revolution” was underway. In the early 1950’s, Watson and Crick revealed the double helix structure of DNA, an event that ushered in the era of direct study of genes and impacted virtually every area of research in biology. At about the same time, Peter Medawar in Britain and Macfarlane Burnet in Australia each made seminal contributions that revolutionized our understanding of the immune system and led to a remarkable expansion of fruitful research in immunology.

The two fundamental riddles that the immune system presents are:

How can it recognize and respond specifically to an almost infinite array of antigens (bacterial, viral, even synthetic molecules)?

How does it normally avoid responding to “self”, that is, to antigens in one’s own make-up, while rejecting those from another individual?

Burnet and Medawar opened the way to answering both questions. Remarkable contributions by many outstanding researchers have since proven them correct and revealed vital, previously unknown, features of our immune system. In proof of Burnet’s “clonal selection” theory, it has been shown that each of our many billions of immune cells is restricted to making a unique antibody molecule or antigen-binding site. When activated by a particular antigen, the cell multiplies, resulting in a clone of cells that that will respond when exposed to the antigen. Medawar (and Burnet) also postulated “acquired tolerance” to “self”, whereby cells that could target self-antigens are destroyed in early stages of development. Indeed, as later discovered by Miller, that’s exactly what happens in the thymus, an organ whose function had been a mystery. Medawar’s experiments and insights paved the way for significant medical advances, including in organ transplantation.

Very exciting things happened during my almost thirty years in immunology. Some I recognized and marveled at as they unfolded. Some I took note of, but underestimated. In fact, the Davis book is most inspired by an area of research whose initial phases I found confusing and tended to overlook: the very intriguing and important place of variable histocompatibility sites on cells of the immune system and possibly the brain.

My intent here is not to attempt an even meager review of progress in immunology during and after my active connection. I only want to share some reflections.

I’m struck by the enormous creativity in scientific endeavor, no less than in art. The difference from at least most great art is that creative achievement in science is a collective experience, more than the imagination and genius of any one brilliant talent. Big ideas and small by many, many investigators, and lots of hard work, go into every important discovery and its verification. When the pieces come together, from many people in many lands, it’s a thing of beauty and a triumph of human creativity. The canvas is vast and the minor brush strokes by most contributors are soon lost from view.

My colleagues and I shed a little early light on the make-up of an antibody combining site, not of lasting consequence once the full picture emerged after it became possible to work out the complete structure of genes that code for an antibody molecule. That was achieved by Susumu Tonegawa, a Japanese scientist. Yet we had our moments and I can still feel each thrill. Of course, there is also chagrin when I think of a smudge or two we added inadvertently to the canvas by misinterpreting an experimental result.

Back to the Davis book, much about the significance of compatibility genes was new to me and impressive. Things have come a long way since Zinkernagel and Doherty discovered in 1974 that, in order to kill a virus-infected cell, an immune cell (a T cell) had to recognize both a viral antigen and the targeted cell’s major histocompatibility marker. The implications of this finding have become increasingly important in medical and genetic research into patterns of susceptibility to certain diseases.

Davis is most excited by the discovery that histocompatibility genes function in brain. That was bound to evoke great interest in further research and a lot of speculation as well. Davis and others are especially fascinated by a so-called “dirty T-shirt” experiment, where women are turned on by smell to the discarded undershirts of men with appropriately matched or unmatched histocompatibility genes. Davis embraces with enthusiasm the possibility that sub-conscious responses to histocompatibility types may be determining whom we choose to love and other fateful decisions.

Forgive me for being old fashioned, but this isn’t our first exposure to absurd theories of genetic determinism.

Still let’s not on that account minimize the established importance of compatibility genes. I should probably maintain humility regarding some (not all) speculation on connections between the immune system and the brain    — after all, during my time in immunology, I regretfully managed not to be much distracted by significant phenomena like histocompatibility, NK (natural killer) cells, and more.

So, thanks to Davis for making my fond ties to immunology vivid once more.

"TWELVE YEARS A SLAVE"

I’ve neglected my OpEd page for the last few weeks, but I’ve been on a rewarding binge of book reading: Twelve Years a Slave, Solomon Northrup; The Compatibility Gene, Daniel M. Davis; To End All Wars, Adam Hochschild; The Burgess Boys, Elizabeth Strout; and The Nose, Nikolai Gogol. They were all worth the time, though not equally rewarding.

I’ll comment briefly on the first today and get to the second, the  gene story, later on.

Having read Twelve Years, I have now seen the movie as well. The book is remarkable. Northrup describes his experiences, his deepest emotions and reflections in the struggle to survive his captivity into slavery. Still, his dignity is never surrendered. His powers of observation are not dulled by whippings, acts of barbarism and humiliation. What survives his 12 years, and is recounted in his book, is a deep understanding of all aspects of the slave system and its impact on the human beings who inhabited that world. He understands people, differences in experience and reactions among those enslaved and among “masters” and families brutalized and corrupted by slavery.

The book’s depth and authenticity rank it in my opinion with Frederick Douglass’s narrative of his life as a slave. The movie is a noble achievement, but there’s no way the richness of Northrup’s account can be captured in a couple of hours of a movie. The movie should be seen by millions of Americans. Some will avoid it because they don’t recognize the great weight of slavery on our history and its impact on present-day economics, politics and so many, many lives. Others may think to avoid it because watching scenes of brutality is terribly difficult. But even if you close your eyes involuntarily from time to time, don’t allow yourself to miss out.