Code Breaker

Battlefield promotion system First twin designer babies, no HIV receptor, by chinese scientists. Mother was suffering from AIDS. Operation was not medically necessary as there are other ways like sperm washing ("Sperm washing can be used to decrease the risk of HIV transmission in HIV-positive males, because the infection is carried by the seminal fluid rather than the sperm." – Wikipedia).

atom, bit, gene wavering, lanky, stymied Keeping grandma's diary cookie cutter house

Watson uses Rosalind's data without permission Darwin was going to be a doctor but he was afraid of blood

Everyone overlooked Mendel's work that discovered how traits are passed through generations

Watson: Hypocrisy in search of social acceptance erodes your self respect

Watson read "What is life?" by Shroedinger, Doudna read "Double Helix"

Watson describes Rosalind's attire in his book

Rosalind disliked Wilkins

Lawrence Bragg, the director of the laboratory, mandated Watson and Crick to stop working on DNA because Wilkins and Franklin were already working on it

Watson and Creak celebrating Pauling's mistake in a bar

Wilson showed Watson Franklin's photo 51 and Watson understood that it can be produced only by the helix. Rosalind did not think so

Watson used cardboard cutouts of molecules to figure out that A pairs with T and C with G

Nobel prize was awarded in 1962 to Watson, Crick, and Wilkins. Franklin died in 1958 from ovarian cancer. Nobel can be awarded to maximum 3 people

Watson leaves the seminar to search for his son Rufus who tried to commit suicide by jumping from WTC and now escaped psychiatric hospital

Introns

Szostak: Never do something that a thousand other people are doing

Jack Szostak invites Doudna to study RNA replication to help prove the hypothesis that RNA was the basic building block of the central dogma: RNA, DNA, proteins

First marriage ended after a few years

Franklin worked on the structure of DNA, Doudna worked on structure of RNA

Randomly meeting Tom Steitz for coffee who mentioned a solution to a problem that Doudna had: RNA breaks down under xrays. Solution was cryocooling crystals

Chapter 8

Two body problem: hire both husband and wife

RNA interference

In E coli there are 1000 base pairs and in the end 5 groups of 29 pairs with spacers in between. Spacers match the DNA of viruses. CAS = Crispr associated enzyme takes the "mug shot" of the virus - incorporates its DNA into bacteria DNA

Chapter 12

Yogurt company has DNAs of all bacteria they've used and funded research to protect them against viruses

Genentech patents in 1974 recombinant DNA technology that was discovered by Paul Berg

23000 pigs and cows, 8000 pounds of pancreas, 1 pound of insulin. First biotech company to launch an IPO, ticker GENE

2011 Doudna and Haurwitz starts a company Caribou (Cas + Ribonucleotide)

After the atomic bomb was done purely by government, Vannevar Bush proposes triangle model: business, government, academia. Governments should not create their own research labs. Later philantropy is added (like Bill and Melinda Gates Foundation). Stanford became the first place where turning research into companies became normal.

Charpentier is a nomad, hates the concept of work-life balance.

in vitro, in vivo First something is done without the isolation

After June 12, 2012 the race is to adopt CRISPR to the human cells (with nucleus)

Tempest, stoke

Competition as a part of normal scientific process

Church is doing an experiment to take a skin cell from a modern elephant, convert it to the embryonic state and then modify the DNA to match the mammoth

How much scientists depend on their students

TALEN by Berg?

codon optimization -- well known technique to adapt bacteria genes to humans by changing codons to get a pass from the immune system

Theory of relativity or transistor were singular advances, CRISPR were a group effort.

Page 213 companies

The Breakthrough Prize in Life Sciences, 3 mln usd for each recipient, by Yuri Milner

The Heroes of CRISPR by Eric Lander of Broad Institute, who is called an evil genius for it. Article barely mentions Doudna and gives many credits to Zhang

"the most entertaining food fight in science in years"

Patents were created in Venice republic in 1474.

2019 first CRISPR treatment for sickle-cell anemia where gene mutation causes mutation in haemoglobin and results in blood cells to be not round, but sickle. For the treatment blood cells are taken from the patient, edited, then reinserted back. They remove a gene that switches the cell from making fetal haemoglobin to haemoglobin A. And the fetal haemoglobin is normal. After 9 months the treatment is a success, the body now makes good hemoglobin cells. To lower the cost you can do edits inside the body, but you need to deliver the editing mechanism with the virus. https://www.youtube.com/watch?v=mQ8Ola_C5po

However gene for sickle cells provides immunity from most of malaria form and this makes it useful for African people.

Turning off myostation that inhibits the muscle growth after the organism is matured. Josiah Zayner.

Anti-CRISPR: viruses can shutdown CRISPR.

Berg, Watson, Boyer signed a letter to create a moratorium on the use of recombinant DNA until guidelines are created. Berg wanted to ban the recombinant DNA because it is too easy to use.

IVF 2010

Why Doudna was shocked to know that babies were born?

Jiankui, only at 34, turns from hero to monster. 3 years in jail, pleaded guilty, 430k fine, banned for life form working in reproductive science.

p. 326: inverted microscope, few thousand dollars for the embryo edits

Test tube 1978

Is it gene replacement? Or cut? DNA gets shorter?

Prenatal testing for the Down syndrome results in 2/3 of abortions.

IVF allows to test and choose eggs for implantation.

Similar line to cross as atomic bomb

Treatment vs enhancement

Huntington's disease -- death of the brain cells

Human Natute documentary 2019

David Sanchez: "I learned how to be positive. I don't think I would be me if I didn't have sickle cell." Miles Davis had sickle cell.

Deaf lesbian couple found a deaf sperm donor and now have a deaf child. Is being deaf a disability? Is being gay a disability?

Gene SLC24A5 has a major influence on skin color. Can black parents modify child's genes to be white?

Eero Mantyranta, olympic skier, hs gene mutation that increases number of red blood cells by 25 percent.

ACTN3 runner gene

Tiger Woods had laser surgery to improve 20/20 vision

Van Gogh, John Nash had either schizophrenia or bipolar.

Eugenics

John Locke: personal liberty is good, different people have different idea of good.

John Stuart Mill: societal good is more important, e.g. masks and vaccine.

p. 357

John Rawls Theory of Justice Robert Nozick Anarchy, State, and Utopia

liberal vs libertarian

Diversity is good for us as a species

Darwin has a list of evolution failures, like inability of humans to synthesize vitamin C

wigits

SARS: severe acute respiratory syndrome

30k base latters in SARS-CoV-2, 3 billion in human DNA

Where is Atlanta? CDC

Swab gets RNA from mucus, then RNA is turned into DNA, then using cooling and heating with polymerase chain reaction produces copies of that DNA, so it makes possible to detect the virus. PCR is invented in 1983.

Human Health Services (parent of FDA) announced an emergency and that blocked all universities and labs in using their own tests.

FDA asked for a printed copy and a compact disc.

Cas12 chops up nearby molecules if it finds the DNA. By using fluorescent molecules, DETECTR is crafted.

1790 Edward Jenner notices that milkmaids are immunte to smallpox, takes cow's pus and rubs it into the cuts on the arm of the 8 year old boy, then exposes him to smallpox.

Attenuated viruses for vaccines are first growed in chicken eggs.

Inovio electric zapper, opens up pores on cell membranes to let the DNA into the nucleus. The DNA then creates messenger RNAs. RNA vaccines do not need to go into the nucleus.

Zayner takes the recipe from Science paper describing DNA vaccine

David Ishee uses CRISPR to make dalmatians glow in the dark.

languid

Dariia Dantseva from Dnipro

microfluidics

p. 462 web app

Follow up

Spacer (virus DNA) is combined with Cas9 protein and tracrRNA (https://www.youtube.com/watch?v=KSrSIErIxMQ). CRISPR-Cas9 cuts, then eukaryotic cell have repair enzymes.

human and plant cells are eukaryotic cells. Cri

Examples of germ cells are sperm or egg cells, they are able to differentiate into different types of cells. Once the cell is differentiated, it is called a somatic cell.

First time Nobel is awarded to only women.

Marie Curie, Rosalind Franklin

How CRISPR works: https://www.youtube.com/watch?v=4YKFw2KZA5o

Isaacson is writing the biography of Elon Musk (August 2021).

Nobel is in October https://www.nobelprize.org/prizes/lists/all-nobel-prizes/

CRISPR is an adaptive defense system against viruses evolved in bacteria. In DNA, there are regions that encode CAS genes (source code for proteins) and CRISPR array (parts of virus DNA). From CRISPR array the crRNA are created which are then combined with Cas9 protein. This complex finds the virus DNA and cleaves it, so the virus stops replicating.

Follow up reading?

1. A Crack In Creation
2. Double Helix
3. Regenesis: How Synthetic Biology Will Reinvent Nature and Ourselves

Human Nature documentary https://wondercollaborative.org/human-nature-documentary-film/

How GMO fruits and vegetagles are produced?

Russians who emigrated https://en.wikipedia.org/wiki/Eugene_Koonin https://vcresearch.berkeley.edu/faculty/fyodor-urnov

Timeline 1962 Nobel prize for DNA

1974 Stanford applies for the Recombinant DNA patent – method to interject 2 DNAs together. It is now used to produce insulin, by inserting human insulin into E. coli (yeast). Genentech is the first biotech IPO. Nobel prize in 1980.

1978 – First child born with IVF

1983 PCR (polymerase chain reaction) – method to amplify DNA by copying it in the test tube

2021 CRISPR paper non nucleus cells