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Profs feel satisfied, snubbed by Nobel Prizes

October 04, 2018
by MADDIE BENDER

STAFF REPORTER, Yale Daily News

Over the past three days, the science world has been held in rapt attention as the Nobel Prizes in Physiology or Medicine, Physics and Chemistry have been awarded.

At Yale, researchers see the prizes as justification of their work, well-deserved recognition of their mentors and, in some cases, snubs of their colleagues’ or their own research.

The Nobel Prize in Physiology or Medicine was awarded to two researchers Monday for their efforts in cancer immunology, a field that seeks to use the body’s own immune system to attack cancer.

Normally, immune cells called T-cells work like sniffer dogs — messenger cells show them a piece of a cancerous or otherwise dysfunctional cell, and the T-cells hunt down and destroy the misbehaving cell. But sometimes, as 2018 Nobel laureates James Allison and Tasuku Honjo found, proteins known as immune checkpoints can stop these T-cells in their tracks, causing them to pass over a cancer cell instead of attacking it. Researchers then were able to develop drugs to stop the expression of two of these checkpoints, called PD-1 and PD-L1.

The development of checkpoint inhibitors, as the drugs are called, drastically transformed the nascent field of cancer immunology in the 1990s, said Mario Sznol, the co-director of the Cancer Immunology Program at Yale Cancer Center.

“The immune system is being able to put your foot on the accelerator, being able to put your foot on the brake,” Sznol said. “In some cases, the signals put the foot on the accelerator but at the same time the brake is on, and so what these drugs do is they take the foot off the brake.”

He added that before Allison and Honjo, scientists had tried without much luck to put their foot on the accelerator. In some cases, checkpoint inhibitors have cured cancer patients of their diseases, something that was considered impossible with the treatments available prior to their development.

Sznol praised the decision to award Allison and Honjo, but said there were many others who also deserved recognition for the discovery.

“One of the people who didn’t get the Nobel Prize but made a major, major contribution to understanding this pathway and its role in the treatment of cancer is Dr. Lieping Chen, who’s here at Yale, and as far as I’m concerned, Dr. Chen also deserves part of the Nobel Prize,” he said.

Chen, the other co-director of the Cancer Immunology Program, said he was “a little confused” about how the Swedish Nobel Committee came to their decision for the prize. Chen is credited with discovering PD-L1, one of the immune checkpoints, which he detailed in a 1999 research paper in Nature Medicine.

However, he said he has already moved on and is focused on advancing science and finding a cure to cancer.

“When the Nobel Prize was announced, I got a little bit uneasy, [which] lasted for about 30 seconds, but that was it for me,” Chen said. “Maybe 30 seconds is already long enough.”

Three physicists were honored Tuesday with the Nobel Prize in Physics for their efforts on utilizing the power of light to manipulate objects. Donna Strickland, who with Gérard Mourou was awarded the prize for her work in high-intensity lasers, was the third woman to be given the prize in physics in its 117 years of existence.

As a graduate student working under Mourou at the University of Rochester in 1985, Strickland co-invented a technique for producing short, high-power laser pulses she called chirped pulse amplification.

When she was a graduate student at Princeton in the ’90s, Yale professor of applied physics Hui Cao shared an office with Strickland, who had completed her postdoctoral research and was employed on the technical staff of Princeton’s Advanced Technology Center for Photonics and Opto-electronic Materials.

“She wasn’t my formal graduate adviser, but we worked in a lab together and she really taught me all the experimental skills,” Cao said. “She was, I would say, my first mentor in a lab.”

Cao recalled a time where, after completing a very difficult optical alignment, Strickland was so happy that she started dancing in the middle of the lab. After all these years, Cao said she still remembers that as an example of Strickland’s outgoing nature.

Strickland and Mourou’s invention of chirped pulse amplification, which stretched laser pulses before amplifying them to create a lower peak power and decrease the risk of damaging the materials lasered, has become “an enabling technology,” Cao said.

Laser eye surgery, for example, depends on this technique. Another proposed application is out of this world, literally. Cao said some scientists have proposed using the invention to divert space debris heading toward the Earth.

“A laser pulse can shoot through it and move its location to orbit, which can eventually move it away from the Earth,” she said.

The Nobel Prize in Chemistry was awarded Wednesday to three researchers who “harnessed the power of evolution” to produce enzymes and antibodies, according to the prize’s press release. Two of these researchers, George Smith and Sir Gregory Winter, respectively described and developed a technique, called phage display.

Phages, which are viruses that infect bacteria, possess a useful characteristic — when Smith inserted genes into the organisms, they translated them and displayed the corresponding proteins on their surfaces. Winter built upon this research, seeing if the same could be done for antibodies — markers our immune systems use to target pathogens.

Bryce Nelson, a professor of pharmacology at the School of Medicine whose lab uses phage display, said the technique is driven by evolution in which researchers construct whole “libraries” containing vast combinations of proteins that could serve as potential antibodies.

After assembling these libraries, researchers can select the proteins they like, tweaking the libraries as they go along.

“That whole process from beginning to end, from the isolation, from assembling the libraries all the way through to selecting the lead candidates, through to maturing them and engineering, really is what we’re talking about as directed evolution,” Nelson said.

Previously, scientists would inject a foreign protein into an animal model and wait months for it to produce specific antibodies, but phage display takes weeks instead, and there is much less of a black box surrounding the process, Nelson said. Additionally, the process occurs in petri dishes and test tubes rather than in living organisms.

While Nelson said he could think of a couple people who might have been included in the prize, he said he was happy for the researchers and for the increased attention the field is now receiving.

“I use phage display to engineer proteins — it’s really about what you do with those proteins afterwards, and without them, I wouldn’t be using phage display, so personally, I’m pretty happy for them,” he said.

This is the second time a Nobel Prize has been awarded for phage research. In 1969, the Nobel Prize in Physiology or Medicine was awarded to three researchers who discovered the replication mechanism and genetic structure of viruses.

Maddie Bender | madeline.bender@yale.edu

Correction: Due to an editing error, a previous version of this article stated that the Norwegian Nobel Committee awards the nobel prizes in Physiology or Medicine, Physics and Chemistry. In fact, the Swedish Nobel Committee awards these nobel prizes.

Submitted by Beth Cadugan on December 17, 2018