Sunday, January 28, 2018

A Look into "Big Science"

The race between private and public industry to sequence and map the human genome marks a monumental accomplishment in history and an interesting tale, described by James Shreeve in The Genome War. Francis Collins was one of the faces of the government’s genome project (officially the head of the National Genome Research Institute) while Craig Venter’s Celera was a private firm. Their techniques to achieve the end goal, time frame, and sources of funding differed, making the story a stark contrast between private and public industry. However, both had the same goal: to unravel one of “the greatest mysteries in all biology.”

With a goal as big as mapping the human genome, one can categorize the project as “Big Science”, a term coined by Alvin M. Weinberg in 1961. Big science is done on a grand scale; it usually involves many researchers working on a project and large sums of money spent, due to massive research thrust. A classic example of big science is the Manhattan Project.  In comparison, “little science” (or small science) is obviously on the smaller scale, usually comprising of only a couple researchers or smaller objectives. This is the typical research done at universities. Example of little science are Francis Crick and James D. Watson’s discovery of the double-helix structure of DNA in 1953 or Albert Einstein’s Theory of Special Relativity.

The Genome War gave insight into the complexities of Big Science, and the components that make up the struggles of tackling such a large project. One aspect that struck me was how expensive the whole Human Genome Project was, as it cost about 3 Billion dollars in total. In my mind, a modern day comparison of government funded research is the BRAIN Initiative – a 100-million-dollar program with the objective of developing new technologies to “uncover the complex links between brain function and behavior.” Both the BRAIN Initiative and the Human Genome Project are big science projects with a lot of tax payer money behind it. What happens when the project doesn’t go as planned? If it turns out to be a dud and the news is released to angry tax payers? N.A.S.A.’s Hubble Space Telescope is a great example.

The cost effectiveness of small science versus big science is an often debated topic, but none the less, both small science and big science are equally needed in research. Small science helps pave the path for big science, resulting in some of the most ground breaking discoveries or uncovering of some of the biggest mysteries in science. The Genome War gives descriptive insight on the endeavors of such a large project such as cost, number of researchers, time spent to completion, development of technologies, and the resulting effect on medicine/science. 

References: 

Shreeve, James. The Genome War: How Craig Venter Tried to Capture the Code of Life and Save the World. New York: Ballantine Books, 2005. Print.

PLAYERS in the SCIENCE game

- Dissecting the stakeholders in the biotech business by studying Craig Venter’s quest to sequence the human genome -

Ask a hundred people who knew Craig Venter to describe him, the first thing ninety-nine of them would say is “brilliant”. That is expected, from his resume, anyone could say that he’s smart. But watching his various interviews, they would immediately follow with the word “arrogant”. The man did take it on himself to decode life and play God after all. Many problems ensued and thus many believe, and rightly so, that Ego would pose many problems to a project as ambitious as that. I would like to, however, argue that it will take an ego that big, an immovable belief in its eventual triumph to help a man achieve wonders in this society.

Venter stands as a man larger than life. The public either adored and admired him as a maverick, or hated and feared him as the Devil himself. Yet, I see a man with multiple leashes on his necks, struggling to navigate in between demanding stakeholders, who with one action could ruin Celera.

1. The science guys:

First introduced in the book, in 1998, the scientific community was sturdy on its way to accomplish the Human Genome Project. Slowly but steadily, the coordinated attempt from the US, Japan, Germany, France, Canada and China abided by the Bermuda standards, which value accuracy and unity over speeds and efficiency. Venter started Celera, the private sector’s attempt to sequence the human genome, during this period; and sure enough, the two came crashing head to head.

To the scientists working on the HGP, Venter’s effort was a blow to the face, a betrayal of all their values. Venter announcing the effort to the public alone could cause the funding for the HGP to diverge and decrease.  If Celera finished the sequencing before the HGP, all the funding to HGP for 8 years then would have been wasted. Funder would then be more reserved and alarmed and might just decrease or even diverge funds for the HGP. The existence threatened, the HGP decided to sacrificed a bit of its own moral high ground (the Bermuda standards) to focus on speed to publish more to the public first, all to prove its worth.

Of course, the fundamental differences were the methods the two used. HGP preferred the trusted Sanger sequencing while Celera put their money on the controversial shotgun sequencing. But this was the matter of pride. Venter did try his best to be humble, wanting to cooperate. Francis Collins, the head of the project, so sure of his own judgment, publically stating the alternate method to be unreliable. Additionally, Craig poached (and definitely needed to) some of the talents working on the project to work for him, so the heat worsened. Competitiveness has always been romanticized and idealized in the US. It sure did its jobs, and now both parties would have to race against time and each others, meanwhile sacrificing the chance for maximum efficiency.

2. The cash cows:

To build infrastructure and acquiring the machines and talents needed, a business needs capital. And capital means responsibilities, as Venter would have to juggle the demands of Celera owners.

The first obvious candidate was the US government. Basically the biggest business in the world with the deepest pocket, making money from 320 million taxpayers, the government has to take the responsibility to fund large scientific projects such as this. In this case, the Department of Energy already funded the HGP, and also shook hands with Venter behind Collins’ back, understanding where the most beneficial position for the government would be. The DOE, too would demand results, and hopefully any cooperation between its competitive sons to save face with the public. As said, Celera struggled to obey, and eventually failed miserably.

The second source of funding is the venture funds who put their faith onto Celera. Particularly, Celera paid its first paycheck to its employees with money from the Perkins-Elmer Corporation. The mother company, represented by Tony White, made sure to engrave onto Venter’s brain of his responsibilities to shareholders: Returns from investment or Growth in net worth. From a corporation’s standpoint, not any of its individual, it wouldn’t want to pursue any grandiose mission to save humanity, it would simply want to make happy for its board members and see its stock grow in value, which is particularly tricky because the decision to bring Celera public.

The invisible hand of the market moves unpredictably and the generic stock traders reacts erratically. Yet, stockholders always want to see their numbers green and above their options’ price. Venter had to tour around the country and sang just to get people to understand what he was doing, not mentioning buying it. After the IPO, Venter had to make sure Celera’s face is clean and smiling to keep the public calm enough to not act too radically.  Any scandals, any leaks or a dip in the revenue chart could mean the end of Celera’s cash flows.

And the ones who were hoping for the effort to succeed the most was the clients, both guaranteed and potential. So basically humanity. The big pharmaceutical companies would be the first to bet on the Celera, having enough cash to handle the risks and enough greed to want to make more. Celera had got its first clients: Amgen, Pharmaceutical Upjohn and Norvatis, paying 25 million dollars in one go, when Venter’s crew hadn’t even got the machines started yet. Venter’s career would be on the line, if Celera went bankrupt. Not to mention, hundreds of thousands of labs and researchers had been longing for genetic date for their own researches. Plus, an infinite number of humans yet to be born could use the information to fix their genetic deflects. For Venter’s crew to visualized, Venter coined the number: “A hundred million customers”

3. The “hungry” mob:

They are not particularly angry, but always thirsting for information. They build statues and the next minute, point torches and pitch forks at the same hero. The outsiders remain outside of the operation, but always have a say in what’s “good” and what’s “bad”.

The press gets to portray the company. Missed a step, and the media can smell it and transcribe it straight to its consumers. A little bias here, a little mischaracterization there, and the public can turn hot to cold in one note. Venter had better foster good friendship with the press.

Yet, its just a tool to the true master of the company. Since its conception, with the power of many, the public could bend corporations to its will, sometimes intentionally, using boycott, protests and influencing politicians, and sometimes unintentionally. For a man who hasn’t act selflessly once in his entire life, it would be hard to imagining him not patenting all of the human genome and make billions out of it. But Venter chose not to, and intended (or at least tried) to release the date to the public instead. One could easily argue that he tried to do so because he wanted to be loved by the public, to be seen positively. Which would only have mattered if the public deemed a public genetic database to be in its best interest and morally right. Plus, the public decides the stock price.

Thus one of Venter’s duty is to remember to pat the public on its head to make sure Celera is seen in the best light possible.

4. The team:

At last, to build, to discover, to create, to do anything at all, one always need to good team. Venter had to make sure he’d got the best people in Celera and get them to co-operate. Venter wasn’t the only one taking pressure from the aforementioned parties, because his subordinates had eyes and ears, too. They also understand the magnitude of this effort in the course of history, and that alone could render humans numb with fear and anxiety. Thus, one more final line in Venter’s job description was to boost the employees’ morale.


In conclusion, any man courageous enough to take the burden of a task this herculean needs an equal size ego and intellect to take the heat that comes with it. In the old days, scientific breakthrough could have happened with Faraday alone in a lab with a bunch of aluminum wires. But for a breakthrough that requires massive co-operation, it takes a village and a man just a little bit too arrogant for his own good.

The Cross-Section Between Capitalism and Science

The Human Genome undeniably has many positive and negative consequences to whoever’s hands it would land in. In one stratosphere, scientists will have unearthed the very essence that makes a person tick; they will have in their hands the very code that creates the physical characteristics, personality, and underlying biology in every single person that will ever exist. However, at the complete opposite end of the spectrum, private capitalistic companies also may decide to invest time and energy to unearth human’s mystery, but may also take complete control over access to such a coveted sequence of letters. If it had fallen into the wrong hands, science could have come to a complete halt—medicine left to its own devices—had the genome been tainted with greedy, egotistical company giants.
                Craig Venter presents an interesting cross-section between both separate worlds. Raised as a scientist, but with the ambition of a CEO, Venter posses the ability to bridge the gap and highlight and meld the better characteristics in both worlds. Like any new and upcoming trend-setter, Venter would have to experience the negative backlash, naysayers, and even unseen obstacles, but given his heart and determination, he could bring to light the backbone of the human race while still running a private company. Undoubtedly, private companies such as Celera have more leeway and budget to work with in comparison with federally funded organizations, so they are able to delve more deeply into this topic and invest more money. These unrestricted abilities thus allow for quicker development of machines and other discoveries than if federally funded organizations had the same goals.
                However, while money sits at the basis of every private company, it becomes hard to invest millions, if not billions, of dollars into research that may terminate with no monetary value if funded by a large company. For instance, when Craig Venter partnered with ABI, his open-access and honest research became hindered for the sake of turning a profit and making sure there was money in place of the “light” at the end of the tunnel. Unfortunately, most people are unlike Craig Venter when it boils down to true honesty and desire to improve the scientific world without the traditional research path. Capitalism thrives off greedy, egotistical giants who care nothing more than using the work of others to turn a quick profit. Had Craig Venter switched mindsets and desired nothing more than stocks or patents off the Human Genome in place of his unrestricted access mantra, the world would have to pay the dire consequences. Capitalism could have ruined genetic therapy, gene editing, and the future techniques to come from unearthing the greatest gem of the 20th and 21st centuries.
                If capitalism and science were to ever intersect again, it would take a person like Craig Venter to combine them beautifully with little to no severe consequences. Science runs off of honesty and free-access, however capitalism strives to restrict access and drive competitive prices. The two obviously do not innately mix; they are just like oil and water. Yet capitalism solves the problems science poses such as limited budgets and restricted opportunities set by the federal government, so in a way they compliment each other. If scientific integrity and honesty could exist within the capitalistic sphere, science would benefit immensely from the lifted barriers and bigger budget. 

Shreeve, James. The Genome War: How Craig Venter Tried to Capture the Code of Life and Save the World. Ballantine Books, 2005.

Interference: Monetary Motivations Among Research Endeavors

Craig Venter is repeatedly vilified throughout The Genome War for many different and somewhat conflicting reasons. It seems that if he's not being called out for his personality he's being critiqued for his work ethic and style. This brings to light a certain attitude about the scientific community I hadn't previously noticed: if you have any monetary motivations, even if they're inadvertent, they can be held against you.
It's not that I can't see the point of view of the other scientists involved in the race to complete the "code of life", a holy grail of sorts for the scientists during the time period of James Shreeve's book. I'd love to have a world where scientists can just complete research without anyone trying to jump on it immediately for profit, or direct benefit. Especially as was the case with the human genome: something that holds lots of connections to many fields of life science should be free in a perfect world. 
But the world isn't perfect. 
Seeing business in something that's not inherently business related is something that happens all the time in all fields of study. And reading about Craig, our almost main character in this real life story, I was off put by just how harsh his peers were when it came to his attempts to make light business out of providing information. People go to work to get paid, and at the end of the day I don't think making money so you can provide for yourself is such a bad thing. 
It's even obvious Craig isn't a true villain, as he's been put through the wringer before with previous business relationships.  As talked about in the book, he broke his past relationship over issues of withholding information to the public to excessive degrees as a cash grab. I personally think that while he does have an abrasive personality and large sense of ego, this fact of making some monetary gain on the side of research isn't the worst thing for people to do-- after all, even scientists have to eat. 

References
Shreeve, James. The Genome War: How Craig Venter Tried to Capture the Code of Life and Save the World. New York: Ballantine Books, 2005. Print.

Craig Venter: Team Player?

Ego aside, Craig Venter truly had his team's best interests at heart. Throughout most of the book we were only given glimpses of Venter through the filter of his ego; How he was looked at from the academic community, from his competition, and from those he did business with. From this perspective he came off as cold and selfish, without regard for anyone else. However, every once in a while we were given a glimpse of the man behind the ego. Venter was a leader. He inspired those around him and pushed those he employed further than they ever imagined. He was able to build a team of the best and brightest and he recognized that.

"Venter liked to say his greatest talent was hiring people who were smarter than he was." (Shreeve, 137) This was our first glimpse of humility from Venter. He recognized the expertise of others and used their skills to build the most comprehensive organization possible. Not only did he find scientists good at their jobs, he found scientists with a reason to prove themselves. This meant they had passion, and if they failed it was their reputation on the line. As evidence, Venter had managed to scrounge up both Hamilton Smith, known as the best bench scientist in the field, and Gene Myers, the brains behind the shotgun method of mapping the human genome. The two men were crucial to the mapping of the human genome.

But even more important than his knack for hiring the best was Venter's ability to keep his team's morale so high. Every way you looked at it, Venter and everyone else at Celera should have been stressed beyond belief, but Venter's unparalleled optimism and high spirits were contagious. On top of his positive outlook, Venter was able to pick up on just how far his employees could be pushed before they reached their breaking point. When he realized Gene Myers was far too worried, Venter invited him out to a race on his yacht. This shows his ability to build a team and then sustain that team until they cross the finish line.

If nothing else, Venter was a leader, and a great leader at that.


References
Shreeve, James. The Genome War: How Craig Venter Tried to Capture the Code of Life and Save the World. Ballantine Books: New York, 2004. Print.

The Man in the Shadows

I have found one of the more interesting people in James Shreeve's The Genome War to be Eugene Myers. Myers is the man behind the code that processed and assembled the genetic data produced from Celera's load of sequencers. He spearheaded the team that came up the idea for the algorithm and then the code itself. This code was arguably the most important piece of Celera's research operation. Without the code, all Craig Venter's team of scientists would have had was strips of raw genetic code generated by the sequencers. Myers code allowed Celera to have a genome instead of scattered genes.

Myers was an important figure not only because of his work on the code. He coauthored a paper with Jim Weber about the whole genome shotgun sequencing technique. This original idea was partly Myers' brainchild. He was cast out by the public project for thinking such an ambitious method could provide the quality of results they were looking for. Venter's ambition and resources allowed Myers' idea to be fully realized. Not only was it possible to use the whole genome shotgun method but it was astoundingly accurate due to Myers' computer program.

Gene Myers had a hand in every step of sequencing the genome. He had an idea for how it could be done. He developed the process to make it possible and he sold it the academic community in a way only a man passionate about his work could have. Gene Myers was the true champion of the whole genome shotgun method. He did not follow the idea as a fad as Craig Venter did, giving it support only after his ambitions outreached the confines of his lab. Myers stood by his opinion and gave the method his full support through its fruition. Myers needed Venter only as a way to fund the project and be a public personality. Venter took care of the public, the money and the business people he involved. Myers was the head of the academic efforts of Celera. This is proven especially true after the company's evaluation of Craig's spending. Venter had more fun hyping his pet project than actually working on it. Myers put blood, sweat and tears into developing his code and defending his idea everyday, hardly stopping to rest and nearly sacrificing his marriage.


References

Shreeve, James. The Genome War: How Craig Venter Tried to Capture the Code of Life and Save the World. Ballantine Books: New York, 2004. Print.

Yang, Sarah. Gene Myers, computer algorithm pioneer in human genome sequencing, to join UC Berkley faculty. University of California, Berkley. 29 Oct. 2002. Web.  http://www.berkeley.edu/news/media/releases/2002/10/29_Myers.html

The Republic of DNA: Politics in Science

James Shreeve's book The Genome War unveils the history of one of the most ambitious projects in molecular biology: decoding the human genome. Referred to by many people in the book as "the code of life," the concept indeed sounds breathtaking. Many people heard of The Manhattan Project (even one of the decoding machine projects in the book bears the same name), but, unfortunately, quite a few people have heard about the Human Genome Project. Yet, in my opinion, the impact of having an “address book” every single human gene is just as profound. 
The book raises many interesting topics behind the narrative of the ambitious project. It reveals a very important side of the matter which a lot of people don’t see behind the headlines. The world of science today is a very competitive, political and sometimes dirty environment. The advance is driven by the human ego, money, and vanity. Many people imagine the world of science as a romantic world of masterminds committed to solving the problems of humanity and the universe. For better or worse—Mr. Shreeve proves that it’s not true.
The economic and political freedom of the United States made it a thriving heaven for scientists. In the competitive capitalistic environment, however, it is often really heard to pursue pure scientific curiosity, it must be a product that can be sold. In some extraordinary cases, like with the Human Genome Project, the government steps in and offers substantial funding. A group of world-renowned scientists gets together and decides on the project plan and starts working on it. What could possibly go wrong? It turns out, a lot of things.
Mr. Shreeve emphasizes the importance of the human ego in science, and that’s exactly why Craig Venter decided to disrupt the delicate balance of the situation and take over the ambitious project. Obviously, everyone would like to just casually mention, “Yeah, I decoded the human genome.” Is he the villain or the hero? It’s up to the reader to decide. In my personal opinion, Celera’s attempt to “patent” human genes shows the crooked intentions of Venter and his company.

Is there a solution to this? Well, the modern economy of the United States doesn’t allow any room for any other approach. The scientific advancement would greatly benefit from additional government funding. If even a quarter of the money spent on the military could be put into the National Science Foundation and the National Institute of Health, the scientific community could get the support and funding it needs. If the most non-scientific aspect of the issue is taken care of, scientists could focus on pursuing real knowledge that could help people, and not waste time on politics, business, diplomacy and backroom plots. If politicians (unfortunately) don’t have to be scientists, why do scientists have to be politicians?