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Louise Chow - Cold Spring Harbor Laboratory’s (CSHL) Women in Science and Engineering (WiSE)

1/25/2025

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Editor’s Note: Professor Louis Chow was selected as one of the recipients of Caltech’s 2024 Distinguished Alumni Awards for her pioneering research using electron microscopy to determine genome organization and RNA transcription, which led to the Nobel Prize-winning discovery of split genes and RNA splicing, one of the most important breakthroughs in molecular biology, as well as for research that has opened doors to improved diagnosis and treatment of human papillomaviruses. We reproduce this article to congratulate and to show our respect for her.

You might have heard about the molecular imaging technique cryo-electron microscopy (cryo-EM) because of the 2017 Nobel Prize in Physics. This WiSE Wednesday we’d like to tell you another story involving a Nobel Prize and electron microscopy (though not the cryo kind). In many ways, this story has striking resemblance to a more well-known story of a woman being denied a share of a Nobel Prize for her work. You might know the story of how Rosalind Franklin got the “pictures” of DNA used to solve its structure that earned James Watson and Francis Crick the Nobel Prize. But did you know that Louise Chow took the images that led to her collaborator, Richard Roberts winning the Nobel Prize in Physiology of Medicine in 1993 for the discovery of RNA splicing?
 
Louise Chow was born in Hunan Province, China and got an undergraduate degree in Agricultural Chemistry from National Taiwan University before moving to the United States to pursue a graduate degree in Chemistry from the California Institute of Technology. Her thesis work involved developing techniques to use electron microscopy to visualize gene organization in bacteria and bacteriophages (you might remember “phages” from last week’s profile of Martha Chase).
 
After graduating, she took a post-doctoral position at the University of California, San Francisco (UCSF), and then joined Cold Spring Harbor Laboratory (CSHL) in 1975 with her husband and fellow scientist Thomas Broker. It was here at CSHL that she performed the groundbreaking work that undoubtedly was crucial to “Robert’s” discovery of splicing, and for which many people believe she deserved a share of the Nobel Prize.
 
In order to make a protein, the DNA in genes is first copied into an RNA intermediary called messenger RNA (mRNA). Initially, this RNA contains “extra segments” called introns between the “exons” that actually code for the protein. RNA splicing is the process by which the introns are removed to make mature mRNA that can be translated into functional protein. Chow and Roberts working at CSHL and Phillip Sharp and his team working at MIT independently discovered this process in 1977. Using electron microscopy methods she’d been perfecting for years, Chow set up the experiments and took images that directly showed splicing taking place.
 
The finding was revolutionary, and an eventual Nobel Prize was almost a given. But whom to award it to? It was agreed that Roberts & Sharp would share pieces, and many people felt that Chow also deserved a share. But, the argument went, if they gave Chow a piece, wouldn’t they have to give Susan Berget, the electron microscopist working with Sharp, a share? And you can’t split a Nobel 4-way, so the men deciding whom to nominate decided to exclude Chow rather than incite controversy over why they chose to award one woman but not the other.
 
Chow and her husband (and vocal advocate) Thomas Broker left CSHL in 1984, continuing their collaborative work on human papillomaviruses (HPV) at the University of Rochester School of Medicine in 1984 and later (1993) at the University of Alabama at Birmingham (UAB). One of Chow’s major breakthroughs in this HPV research was developing a way to produce large amounts of the virus in the lab and study its replication process in tissue cultures. In addition to her work in the lab, she is an Associate Editor of Virology and a member of an NIH advisory committee that reviews gene therapy protocols. She was elected to the National Academy of Sciences in 2012.
 
I had the great privilege of hearing Chow talk when she came to CSHL for a meeting honoring the 40th anniversary of the splicing discovery. I can’t give her the Nobel Prize she deserves, but I award her this WiSE Wednesday profile.

A Letter From Professor Chow
​

Dear Vivien, Lily, Sherry and friends,
 
Thank you for your email.  It was a real surprise to hear from you.  I had no knowledge of the cshlwise.org, nor the website story.
 
I am grateful that you all try to tell the history concerning the discovery of RNA splicing. Since 1977, CSHL never acknowledges our EM contribution, crucial to the discovery.  
 
The story as told by the web posting is largely correct. What is not widely known is that Roberts came to us to propose a collaboration to test his hypothesis to explain the many anomalous biochemical results concerning the adenovirus late RNAs observed by several CSHL research units, including his and our labs. At the time, we had extensive experience in mapping Ad RNAs by EM.
 
The Roberts hypothesis goes as follows.  Adenovirus employs part or the whole of a small abundant Ad virus-encoded RNA, called VA RNA, as a primer to transcribe the Ad late RNAs by elongation. “Priming and elongation” has been observed in flu RNAs and has been proposed by others a mechanism to regulated transcription in high eukaryotes.
 
We designed the experiments (that were never done before) and conducted the experiments with some of the material supplied by Roberts lab.    The EM results immediately revealed that Ad late mRNA were generated by RNA splicing, as well as by utilizing alternative RNA splicing and alternative polyA sites.   VA RNA has nothing to do with the genesis of Ad late RNAs.  Further extensive experimentations followed to map the RNA leaders. Then history and facts were altered by Roberts in his successful campaign for the Nobel Prize.
 
By coincidence, I am going back to Caltech next week for my first official event, 51 years after I received my PHD. I was selected by Caltech as one of four recipients of Distinguished Alumni Awards of 2024.
 
It was a completely surprise; out of the blue I was notified by an email. The Selection Committee cited my EM contribution to the discovery of RNA splicing as well our research on human papillomaviruses in the last 40 some years.
Again, thank you all for contacting me.
 
Warm Regards,
 
Louise
 
Professor Emerita
Biochemistry and Molecular Genetics
University of Alabama at Alabama

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2024 U.S. Presidential Election: What Did We Witness?

1/18/2025

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By Christine Mei

The Democrats' Collapse

The outcome of this election can be described by borrowing a phrase from Taiwanese commentator Kuo Cheng-Liang, as the Democrats "losing so badly it's embarrassing." Why did the Democrats suffer such a disastrous defeat? Before the election, mainstream media polls suggested a neck-and-neck race between Trump and Kamala Harris. So why was the defeat so severe?

The Democrats' collapse can be viewed from several aspects. First, the nomination process for this presidential election was far from democratic. Despite showing signs of cognitive decline, Biden insisted on running for re-election, resulting in no real primary process. Biden's performance during the June debate with Trump was extremely poor. To salvage the situation, Democratic establishment figures like Pelosi, Clinton, and Obama forced Biden out of the race and pushed Kamala Harris, an unpopular and inexperienced vice president, to the forefront. Many voters perceived Harris as uninspired, a candidate simply following the establishment's instructions. On critical issues like reducing inflation, handling illegal immigration, and addressing foreign policy challenges such as the wars in Ukraine and the Middle East, Harris failed to propose concrete solutions. Even when Israel, led by Netanyahu, committed atrocities against civilians in Gaza, the U.S. continued its unconditional support for Israel, justifying it as Israel's "right to self-defense." This stance alienated many voters with a sense of justice. In the end, the Democrats could only appeal to voters with the slogan, "We can't let Trump win," hoping they would vote for Harris.

Did this strategy work? More than half the electorate wasn't convinced. Against an opponent like Trump, with his numerous flaws, how did they still lose so badly?

The Democrats' failure was not just about nominating an unqualified candidate. More significantly, the party's leadership is increasingly disconnected from its grassroots base (workers, minorities, etc.). These voters see billionaires getting richer while they face immense pain, anxiety, and despair in a rapidly changing economy—they crave change.

During the 2016 Democratic primaries, Senator Bernie Sanders proposed numerous policies aimed at improving the welfare of grassroots voters, gaining substantial support within the party. Unfortunately, the Democratic establishment believed Hillary Clinton could easily defeat Trump and sidelined Sanders to avoid disruption. Many of Sanders' ideas even garnered support from some Republican voters. His popularity in 2016 reflected a widespread desire for a non-establishment political leader. However, the Democrats failed to address voters' dissatisfaction and anger, which Trump capitalized on with populist rhetoric like "Make America Great Again," winning the presidency.

The Conflict Between Tech Billionaires and the Deep State

This election also revealed an unprecedented high-profile involvement of tech billionaires. The most notable figure was Elon Musk, the world's richest man. Musk supported Trump not only with massive campaign donations but also by leveraging his social media platform, X, to promote Trump extensively. In the final stages of the campaign, Musk personally campaigned for Trump in swing states. Besides Musk, other Silicon Valley giants also backed Trump. These tech billionaires saw their wealth grow an astonishing 50% from pre-pandemic levels but remained unsatisfied. They viewed bureaucratic inefficiency and excessive government intervention as significant barriers to innovation and wealth accumulation.

They believe the entrenched "deep state," composed of bureaucrats and vested interests, is the primary cause of government waste, inefficiency, and overregulation. They advocate for major reforms to government operations and public policy, aiming to "corporatize" government management and dismantle the deep state.

How Do They Plan to Do This?

They propose drastic federal spending cuts. Trump has appointed Musk and another billionaire, Vivek Ramaswamy, to lead the "Government Efficiency Department," tasked with reducing the federal budget by at least $2 trillion. Plans include mass layoffs of federal employees deemed disloyal to Trump, eliminating departments like the Department of Education, and purging agencies such as the FBI, CIA, and Department of Defense. They aim to manage the government as they would Tesla or SpaceX—minimizing bureaucracy and streamlining processes.

Additionally, they seek to completely deregulate industries. Following Trump's election, financial, tech, and cryptocurrency stocks surged, as businesses anticipated less government oversight. Proposed rollbacks include antitrust laws, securities regulations, workplace safety standards, labor laws, civil rights protections, consumer fraud laws, vehicle safety standards, tax laws, and environmental regulations. In essence, the plan envisions a return to early capitalist "survival of the fittest" principles, where only the strongest survive.

Can a Government Led by Trump and Tech Billionaires Succeed?

The deep state, supported by influential donors, lobbyists, media, and other beneficiaries of the current system, will resist efforts to overhaul the status quo. When Musk and his allies implement drastic budget cuts, abolish federal agencies, and loosen regulations, will the entrenched powers simply stand by? They are unlikely to remain passive and will likely resist overtly and covertly.

The next four years are bound to witness intense clashes between Trump's team and the deep state. Both sides will stop at nothing to discredit each other, exposing scandals and secrets. However, will this power struggle address pressing domestic issues like inflation, the inability to revive manufacturing, extreme wealth inequality, racial conflicts, and homelessness? Will it make America great again?

Perhaps this confrontation will reveal previously concealed truths, such as:
  • The assassination of John F. Kennedy
  • The true story behind 9/11
  • The origins of COVID-19 and the development of vaccines
  • The flow of U.S. aid to Ukraine during the Russia-Ukraine war
  • The military-industrial complex's dealings with the government
  • Corruption among government officials

​If such truths come to light, allowing Americans to awaken to the lies perpetuated by the government, mainstream media, and financial elites, they may demand genuine systemic reform. Only then might the U.S. become a true democracy that prioritizes its people. Here's hoping that day comes soon.

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Capitalist Military Industrial Complex Driven Hegemony Is a Road of No Return

1/11/2025

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Dr. Wordman
 
Capitalism is an important principle in economics. The important elements of economic productivity (production capacity) are manpower (including human labor and human intelligence), resources (including natural water, land, mines, energy, and biology), capital (the tools of trade beyond the era of barter transactions, the value measurement of products and production capacity, and the catalysts for production and consumption), markets (including gathering places of manpower, consumer, and capital, such as factories, mines, stores, and financial centers) and transportation (including water, land, air, electricity, communication, and information data). Capitalism puts capital at the top of economic elements, so there is a saying that no money no business. Capital has a catalytic effect, but it is by no means a panacea, nor is it the only major contributing factor in the economy. When starting an economy, the above-mentioned elements (or factors) all serve different needs, and the needs of different components vary according to the time, place, and environment. When the economy grows, the required contributing elements may also change due to time, place, and people changes. The accumulation and catalytic effect of capital will greatly impact economic development. This is the reason why capitalism cannot be totally rejected. But capitalism will also cause a serious social problem;, capital will likely be accumulated in the hands of a few people. That is, capital will become larger and larger and become more and more concentrated, resulting in a huge gap between the rich and the poor. Then, society cannot be balanced and remain harmonious. In the end, many social problems will arise, causing social unrest and instability. Therefore, capitalism cannot be promoted without regulation.
 
America is a powerful capitalist country. There are many natural reasons why it has become the world's most powerful nation in less than 250 years since its establishment. Political scholars, economists, and historians have done many professional studies, analyses, and comments, but often professional theories do are not applyicable directly to complex, national, and global economic changes in the world, such as the current economic situation under the influence of the US-China competition. The present U.S. national security strategy and economic planning are more influenced by ideology than based on any thorough professional studies. So, there are different voices, even opposite opinions at home and abroad. The social and economic conditions in the U.S. are full of problems and few solutions. The U. S. economic status as the world's number one economy is precariously unstable and being challenged. In contrast, China and other countries are developing rapidly in their economies. The social problems in the U.S. are not just divided opinions but are exhibited by torn social fabrics. These social problems and phenomena can be traced and analyzed following the founding history of the U.S. and the evolution of its political and economic system. The U.S. is a country that practices and protects capitalism, any program initiated by socialism is carried out and managed by a capitalist system. (For example, the social security system or any retirement system.) We can observe how capitalism played a role in the U.S. as it grew, peaked, and declined in its 250 years of history and explain why the capitalist military-industrial- complex- driven hegemony would eventually lead to a road of no return.
 
It was a very lucky and smooth process for the U.S. to launch a revolution resisting high taxation to gain independence from British colonial control. In just a few years, the U.S. got rid of the control of the British Empire. In comparison, China’s revolutionary tofor establishing a republic nation took nearly a century of struggle under the oppression of the great Western and Japanese Imperial powers. During the eighteenth to the nineteenth century, various political and economic ideologies flourished, and the U.S. adopted capitalism and the democracy of people-elected governments. But its road to power mainly owes to the following factors. First, the U.S. is centrally located in the North American continent, a vast land with abundant resources. Second, the U.S. is well protected by the Atlantic Ocean on the East Coast and the Pacific Ocean on the West Coast, away and free from disputes and wars in Europe and Asia. In the two world wars, the U.S. was able to stay out of conflicts to earn war money by trade and join the wars later to receive victory dividends. As a result, the U.S. economy has become the number one in the world, and the U.S. industries, agriculture, manufacturing, and commerce are all leading in the world. All the economic factors in the U.S. are strong, and nothing lacking. Coupled with the catalyst effect of capital, the US economy once reached 40% of that of the world. However, under the impetus of extreme capitalism, the U.S. naturally or greedily prefers the highly profitable military industry, creating the world's largest military-industrial complex, pursuing hegemony, and controlling the world with military (industrial) power and military alliances. If it weren't for the other military hegemony, the Soviet Union, the U.S. would have become the sole global hegemon long ago. The disintegration of the Soviet Union in 1990 was caused by its failing economy. If the military-industrial complex could not make enough money and only had war consumption, it would naturally drag down the economy. That's why the Soviet Union collapsed. Although the U.S. won the Cold War against the Soviet Union, its military-industrial complex could not completely support the U.S. hegemony strategy alone with other industries being neglected, so the U.S. economy eventually declined to 20% of the world's economy. On the other hand, China's economy has risen to 17-18% of the world's economy while maintaining three times or greater than the U.S. economic growth rate (GDP).
 
If the major changes in the world are not caused by wars (World War I and World War II) but by natural disasters, such as earthquakes, floods, fires, and epidemics, the U.S. may also develop into the world's strongest power. It may become the world's major food supplier, the global medical provider, and not a military hegemony. Perhaps the world will not have as many wars as there have been after World War II. The economy needs capital, and capital stimulates the economy as a catalyst. It is a pity that the U.S. has embarked on the road of military-industrial-complex- driven hegemony; since this is a road of no return. It is easy to understand why the U.S. wants to sell arms for high profit, and why it wants to start wars forced by the military-industrial complex. But arms consumption is a negative factor for human prosperity. (War creates negative productivity.)  Eventually, humans suffer and disappear. The U.S. national strategy today is very similar to thea life of a drug addict who knows that drug use is harmful, but too addicted to quit. The U.S. national debt is getting bigger and bigger, and the U.S. society is getting increasinglymore and more torn apart. This is the consequence of capitalist military-industrial-complex driven hegemony. The reason is not difficult to understand. All countries in the world should understand this truth. The U.S. must be persuaded to take a rehab and stop going down this road of no return. China's economic growth has a rational gene of “lifting people out of poverty and providing opportunities for gaining wealth”. Facing the pressure of competition between the U.S. and China, we must rationally learn from the past (the Soviet Union collapsed because of military-industrial-complex hegemony) and accept our present reality (the U.S. is seriously in debt, $100,000/person). We must give up our addiction to  capitalist military-industrial-complex- driven hegemony to embrace cooperation for mutual benefits.
  
 


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